</head><body>Because AT1R seems to be essential for Ang-II–mediated ACE2 internalization, we also tested whether ACE2 and AT1R physically interact. Coimmunoprecipitation experiments confirmed this dimerization in control conditions (Figure 5B, second lane). However, Ang-II treatment decreased this interaction in a time-dependent manner [...]. PMID:25225202 </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re98"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:25225202" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_csa5"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa30" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_csa5_in_0" /><qual:input qual:qualitativeSpecies="sa38" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_csa5_in_1" /><qual:input qual:qualitativeSpecies="sa45" qual:transitionEffect="none" qual:sign="negative" qual:id="tr_csa5_in_2" /><qual:input qual:qualitativeSpecies="sa40" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_csa5_in_3" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="csa5" qual:transitionEffect="assignmentLevel" qual:id="tr_csa5_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><or /><apply><and /><apply><eq /><ci>sa30</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa38</ci><cn type="integer">1</cn></apply></apply><apply><and /><apply><eq /><ci>sa38</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa40</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa45</ci><cn type="integer">0</cn></apply></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body>Recently, ACE2 was reported as an entry receptor for SARS-CoV-2. In this study, we present the crystal structure of the C-terminal domain of SARS-CoV-2 (SARS-CoV-2-CTD) spike (S) protein in complex with human ACE2 (hACE2), which reveals a hACE2-binding mode similar overall to that observed for SARS-CoV. PMID:32275855 SARS-CoV-2 can use TMPRSS2 for S protein priming and camostat mesylate, an inhibitor of TMPRSS2, blocks SARS-CoV-2 infection of lung cells. PMID:32142651 </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re102"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:32275855" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:uniprot:P0DTC2" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> <rdf:Description rdf:about="#re150"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:32142651" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:uniprot:P0DTC2" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_csa9"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa140" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_csa9_in_0" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="csa9" qual:transitionEffect="assignmentLevel" qual:id="tr_csa9_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><eq /><ci>sa140</ci><cn type="integer">1</cn></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body>The G-protein-coupled receptor Mas, encoded by the Mas proto-oncogene, has been identified as an endogenous receptor for the heptapeptide angiotensin-(1-7); however, the receptor is also suggested to be involved in actions of angiotensin II. The study tested whether this could be mediated indirectly through an interaction with the angiotensin II type 1 receptor, AT1. In transfected mammalian cells, Mas was not activated by angiotensin II; however, AT1 receptor-mediated, angiotensin II-induced production of inositol phosphates and mobilization of intracellular Ca2+ was diminished by 50% after coexpression of Mas, despite a concomitant increase in angiotensin II binding capacity. Mas and the AT1 receptor formed a constitutive hetero-oligomeric complex that was unaffected by the presence of agonists or antagonists of the 2 receptors. In vivo, Mas acts as an antagonist of the AT1 receptor; mice lacking the Mas gene show enhanced angiotensin II-mediated vasoconstriction in mesenteric microvessels. These results demonstrate that Mas can hetero-oligomerize with the AT1 receptor and by so doing inhibit the actions of angiotensin II. PMID:15809376 </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re115"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:15809376" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:40674" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa21"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa34" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa21_in_0" /><qual:input qual:qualitativeSpecies="sa71" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa21_in_1" /><qual:input qual:qualitativeSpecies="sa121" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa21_in_2" /><qual:input qual:qualitativeSpecies="sa29" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa21_in_3" /><qual:input qual:qualitativeSpecies="sa136" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa21_in_4" /><qual:input qual:qualitativeSpecies="sa137" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa21_in_5" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa21" qual:transitionEffect="assignmentLevel" qual:id="tr_sa21_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><or /><apply><and /><apply><eq /><ci>sa34</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa71</ci><cn type="integer">1</cn></apply></apply><apply><and /><apply><eq /><ci>sa121</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa29</ci><cn type="integer">1</cn></apply></apply><apply><and /><apply><or /><apply><eq /><ci>sa136</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa137</ci><cn type="integer">1</cn></apply></apply><apply><eq /><ci>sa34</ci><cn type="integer">1</cn></apply></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body>Role_of_spike_ACE2_interaction_in_pulmonary_blood_pressure_regulation_v3.xml) Renin provides only one known function, to cleave the 10-amino acid precursor peptide angiotensin I (Ang-I),1 from the N terminus of mature angiotensinogen (AGT). PMID:10585461 The study characterized Ang-(1-12) metabolism in the serum and kidney of the mRen2.Lewis rat, a model of high circulating renin and ACE expression. Ang-(1-12) processing to serum did not reveal the participation of renin; however, serum ACE readily converted Ang-(1-12) to Ang I with subsequent metabolism to Ang II. Ang I and Ang II forming activities for serum ACE were 102 and 104 fmol/ml/min serum (n=3), respectively, and both products were abolished by the potent ACE inhibitor lisinopril. PMID:22490446 Apart from Renin, several enzymes were found to cleave angiotensinogen into Ang-I, such as cathepsin D (CTSD), cathepsin G (CTSG), and tonins. PMID:30934934 A human neutrophil protease, initially termed neutral peptide-generating protease, has been shown to cleave angiotensin II directly from angiotensinogen and has been identified as leukocyte cathepsin G. When purified neutrophils were disrupted by nitrogen cavitation and fractionated by differential centrifugation, 44 and 24% of the angiotensin II-generating activity was in the lysosomal and undisrupted cell fractions, respectively. The angiotensin II-generating protease of human neutrophils has been identified as cathepsin G on the basis of subcellular localization, substrate specificity, physicochemical characteristics, and antigenic identity. PMID:6172448 </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re14"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:10585461" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> <rdf:Description rdf:about="#re119"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:22490446" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:10116" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> <rdf:Description rdf:about="#re129"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:6172448" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa22"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa21" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa22_in_0" /><qual:input qual:qualitativeSpecies="sa30" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa22_in_1" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa22" qual:transitionEffect="assignmentLevel" qual:id="tr_sa22_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><and /><apply><eq /><ci>sa21</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa30</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body>Recombinant ACE2 hydrolyzes the carboxy terminal leucine from angiotensin I to generate angiotensin 1-9, which is converted to smaller angiotensin peptides by ACE in vitro and by cardiomyocytes in culture. PMID:10969042 </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re9"> <bqmodel:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:10969042" /> </rdf:Bag> </bqmodel:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa23"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa21" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa23_in_0" /><qual:input qual:qualitativeSpecies="sa29" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa23_in_1" /><qual:input qual:qualitativeSpecies="sa38" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa23_in_2" /><qual:input qual:qualitativeSpecies="sa121" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa23_in_3" /><qual:input qual:qualitativeSpecies="sa122" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa23_in_4" /><qual:input qual:qualitativeSpecies="sa144" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa23_in_5" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa23" qual:transitionEffect="assignmentLevel" qual:id="tr_sa23_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><or /><apply><and /><apply><eq /><ci>sa21</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa29</ci><cn type="integer">1</cn></apply></apply><apply><eq /><ci>sa38</ci><cn type="integer">1</cn></apply><apply><and /><apply><eq /><ci>sa121</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa122</ci><cn type="integer">1</cn></apply></apply><apply><and /><apply><eq /><ci>sa21</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa122</ci><cn type="integer">1</cn></apply></apply><apply><and /><apply><eq /><ci>sa21</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa144</ci><cn type="integer">1</cn></apply></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body>ACE2 and ACE catalytic activity has been analyzed in CHO cells expressing human ACE2. ACE converted the decapeptide Ang I to Ang II. ACE2, in contrast, converted Ang I to the nonapeptide Ang1-9. PMID:10969042 ACE2 functions as a carboxypeptidase, cleaving a single residue from angiotensin I (AngI), generating Ang1-9, and a single residue from angiotensin II (AngII) to generate Ang1-7. The ACE2 homologue ACE, by contrast, cleaves the decapeptide AngI into the octapeptide AngII. Thus, ACE2 counterbalances the function of ACE and negatively regulates AngII production. To test whether Spike-Fc injections indeed affect the function of the renin-angiotensin system, AngII levels in the lungs of acid- and Spike-Fc–treated mice were analyzed. Acid aspiration increased AngII levels in the lungs of wild-type mice. Notably, the authors observed a further, significant increase in AngII levels in the lung tissue of mice treated with Spike-Fc. PMID:16007097 Adipocytes express all components of the renin-angiotensin system, and the renin-angiotensin system is involved in obesity and insulin resistance. The aim of this study was to investigate plasma Ang II in obese patients with type 2 diabetes mellitus (T2D) and the change during weight loss. Fifty Japanese obese subjects with T2D were enrolled. After 24 weeks of weight reduction diet, the mean body weight, visceral fat area (VFA), and hemoglobin A(1c) decreased significantly by 2.3%, 7.0%, and 8.3%, respectively. The mean plasma Ang II decreased by 24% and correlated with body weight both at baseline. PMID:19375596 Overall the findings suggest that Ang-(1-12), not Ang I, is the better substrate for Ang II formation by chymase in adult rats. In addition, this confirms the previous observation that chymase (rather than ACE) is the main hydrolyzing enzyme responsible for Ang II generation from Ang-(1-12) in the adult rat heart. PMID:27465904 Since angiotensin-(1-12) [Ang-(1-12)] is a non-renin dependent alternate precursor for the generation of cardiac Ang peptides in rat tissue, the authors investigated the metabolism of Ang-(1-12) by plasma membranes (PM) isolated from human atrial appendage tissue from nine patients undergoing cardiac surgery for primary control of atrial fibrillation. PM was incubated with highly purified Ang-(1-12) for 1 h with or without renin-angiotensin system (RAS) inhibitors [lisinopril for angiotensin converting enzyme (ACE), SCH39370 for neprilysin (NEP), MLN-4760 for ACE2 and chymostatin for chymase]. In the absence of all RAS inhibitor, Ang-(1-12) was converted into Ang I (2%), Ang II (69%), Ang-(1-7) (5%), and Ang-(1-4) (2%). In the absence of all RAS inhibitor, only 22% of Ang-(1-12) was unmetabolized, whereas, in the presence of the all RAS inhibitors, 98% of Ang-(1-12) remained intact. The relative contribution of selective inhibition of ACE and chymase enzyme showed that Ang-(1-12) was primarily converted into Ang II (65%) by chymase while its hydrolysis into Ang II by ACE was significantly lower or undetectable. PMID:22180785 Although angiotensin II (Ang II)-forming enzymatic activity in the human left cardiac ventricle is minimally inhibited by angiotensin I (Ang I) converting enzyme inhibitors, over 75% of this activity is inhibited by serine proteinase inhibitors. The authors report the identification and characterization of the major Ang II-forming, neutral serine proteinase, from left ventricular tissues of the human heart. A 115,150-fold purification from human cardiac membranes yielded a purified protein with an Mr of 30,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Based upon its amino-terminal sequence, the major human cardiac Ang II-forming proteinase appears to be a novel member of the chymase subfamily of chymotrypsin-like serine proteinases. Human heart chymase was completely inhibited by the serine proteinase inhibitors, soybean trypsin inhibitor, phenylmethylsulfonyl fluoride, and chymostatin. It was partially inhibited by p-tosyl-L-phenylalanine chloromethyl ketone, but was not inhibited by p-tosyl-L-lysine chloromethyl ketone, and aprotinin. Also, human heart chymase was not inhibited by inhibitors of the other three classes of proteinases. Human heart chymase has a high specificity for the conversion of Ang I to Ang II and the Ang I-carboxyl-terminal dipeptide His-Leu. Human heart chymase did not degrade several peptide hormones, including Ang II, bradykinin, and vasoactive intestinal peptide, nor did it form Ang II from angiotensinogen. The high substrate specificity of human heart chymase for Ang I distinguishes it from other Ang II-forming enzymes including Ang I converting enzyme, tonin, kallikrein, cathepsin G, and other known chymases. PMID:2266130 This study was undertaken to confirm a previous preliminary observation that hog pancreas kallikrein (EC 3.4.21.35) directly liberated an angiotensin-like substance from human plasma protein Cohn fraction IV-4 at an acidic pH of 4.0-5.0. The amino acid composition of the isolated pressor substance (residues/mol) was: Asp, 1.03; Val, 1.03; Ile, 1.00; Tyr, 0.69; Phe, 1.04; His, 0.91; Arg, 0.86; Pro, 0.86. This composition was identical with that of angiotensin. Since the reaction mixture was not contaminated with common proteolytic enzymes, such as trypsin, chymotrypsin, renin, cathepsin D and proangiotensin-converting enzyme, and other enzymes activated by kallikrein, it is clear that hog kallikrein directly produces angiotensin in vitro. PMID:6555043 </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re3"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:10969042" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> <rdf:Description rdf:about="#re94"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:16007097" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:10090" /> </rdf:Bag> </bqbiol:isEncodedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:uniprot:P59594" /> </rdf:Bag> </bqbiol:isEncodedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:19375596" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> <rdf:Description rdf:about="#re109"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:22180785" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> <rdf:Description rdf:about="#re131"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:2266130" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> <rdf:Description rdf:about="#re132"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9823" /> </rdf:Bag> </bqbiol:isEncodedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:6555043" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa24"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa22" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa24_in_0" /><qual:input qual:qualitativeSpecies="sa100" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa24_in_1" /><qual:input qual:qualitativeSpecies="sa39" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa24_in_2" /><qual:input qual:qualitativeSpecies="sa23" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa24_in_3" /><qual:input qual:qualitativeSpecies="sa30" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa24_in_4" /><qual:input qual:qualitativeSpecies="sa47" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa24_in_5" /><qual:input qual:qualitativeSpecies="sa21" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa24_in_6" /><qual:input qual:qualitativeSpecies="sa121" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa24_in_7" /><qual:input qual:qualitativeSpecies="sa48" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa24_in_8" /><qual:input qual:qualitativeSpecies="sa120" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa24_in_9" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa24" qual:transitionEffect="assignmentLevel" qual:id="tr_sa24_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><or /><apply><and /><apply><or /><apply><eq /><ci>sa100</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa39</ci><cn type="integer">1</cn></apply></apply><apply><eq /><ci>sa22</ci><cn type="integer">1</cn></apply></apply><apply><and /><apply><or /><apply><eq /><ci>sa30</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa47</ci><cn type="integer">1</cn></apply></apply><apply><eq /><ci>sa23</ci><cn type="integer">1</cn></apply></apply><apply><and /><apply><eq /><ci>sa21</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa39</ci><cn type="integer">1</cn></apply></apply><apply><and /><apply><eq /><ci>sa121</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa39</ci><cn type="integer">1</cn></apply></apply><apply><and /><apply><eq /><ci>sa21</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa48</ci><cn type="integer">1</cn></apply></apply><apply><and /><apply><eq /><ci>sa21</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa120</ci><cn type="integer">1</cn></apply></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body>Ang (1–7) can be generated by the action of ACE2 on Ang II or by the metabolism of Ang (1–9) by ACE and NEP (MME) in CHO cells transfected with human ACE and MME. Ang (1–9) was a better substrate for NEP than ACE. PMID:15283675 The main role of ACE2 is the degradation of Ang II resulting in the formation of angiotensin 1-7 (Ang 1-7) which opposes the actions of Ang II. PMID:22536270 ACE2 metabolizes ANG II to Ang 1-7 in the kidney at neutral and basic pH, while prolylcarboxypeptidase catalyzes the same reaction at acidic pH. PMID:23392115 Ang I can be cleaved by NEP (MME) to Ang (1–7) in CHO cells transfected with human MME. ACE and NEP hydrolysed Ang I efficiently, whereas ACE2 hydrolysed Ang I only very slowly. PMID:15283675 Angiotensin peptides are metabolized by several subsequent enzymatic steps: First, renin cleaves angiotensinogen, into angiotensin I (Ang I). Ang I can be metabolized by angiotensin-converting enzyme (ACE) resulting in the production of the bioactive octapeptide angiotensin II (Ang II), which interacts with AT1 and AT2 receptors. Alternatively, it can be processed first by ACE2 to the inactive peptide Ang-(1–9) and then by ACE to Ang-(1–7) or by neutral endopeptidase 24.11 (NEP) or prolylendopeptidase (PREP) directly to Ang-(1–7). Ang-(1–7) can also be generated by ACE2 from Ang II and interacts with its receptor Mas. PMID:23463883. The metabolism of Ang-(1-12) in renal cortical membranes also revealed the formation of Ang I; however, the main products were Ang-(1-7) and Ang-(1-4) at 129 and 310 fmol/mg/min protein (n=4), respectively. Neprilysin inhibition abolished these products and substantially reduced the overall metabolism of Ang-(1-12). Incubation of Ang-(1-12) with either human or mouse neprilysin revealed identical products. PMID:22490446 Ang-(1-7) is the main metabolite of angiotensin I in rat hippocampi, and thimet oligopeptidase is the main enzyme involved in the generation of Ang-(1-7). PMID:24041943 Metabolism of 125I-angiotensin I was investigated. In intact endothelial cells, production of Ang (1-7) was partially blocked by the addition of Z-pro-prolinal, an inhibitor of prolyl endopeptidase. This confirms that prolyl endopeptidase is partially involved in the generation of Ang-(l-7). PMID:1310484 </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re10"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:15283675" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> <rdf:Description rdf:about="#re11"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:10090" /> </rdf:Bag> </bqbiol:isEncodedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:23392115" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> <rdf:Description rdf:about="#re30"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:15283675" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> <rdf:Description rdf:about="#re123"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:22490446" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:10116" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> <rdf:Description rdf:about="#re133"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:24041943" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:10116" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> <rdf:Description rdf:about="#re134"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:1310484" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa25"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa79" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa25_in_0" /><qual:input qual:qualitativeSpecies="sa70" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa25_in_1" /><qual:input qual:qualitativeSpecies="sa23" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa25_in_2" /><qual:input qual:qualitativeSpecies="sa51" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa25_in_3" /><qual:input qual:qualitativeSpecies="sa24" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa25_in_4" /><qual:input qual:qualitativeSpecies="sa22" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa25_in_5" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa25" qual:transitionEffect="assignmentLevel" qual:id="tr_sa25_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><or /><apply><and /><apply><eq /><ci>sa79</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa70</ci><cn type="integer">1</cn></apply></apply><apply><and /><apply><or /><apply><eq /><ci>sa23</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa51</ci><cn type="integer">1</cn></apply></apply><apply><eq /><ci>sa79</ci><cn type="integer">1</cn></apply></apply><apply><and /><apply><eq /><ci>sa79</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa24</ci><cn type="integer">1</cn></apply></apply><apply><and /><apply><eq /><ci>sa79</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa22</ci><cn type="integer">1</cn></apply></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body>Although treatment with AGTR1 antagonist (losartan) or AGTR2 agonist (CGP42112A) inhibits tumor progression in several cancer cells, their combined treatment has not been reported. PMID:25014541 Angiotensin II (ANGII) signaling, mediated via angiotensin II receptor type 1 (AGTR1) or type 2 (AGTR2), controls tissue remodeling in fibrosis, but the relevance of AGTR2 remains elusive. PMID:17630322 Chronic activation of the myocardial renin angiotensin system (RAS) elevates the local level of angiotensin II (Ang II) thereby inducing pathological cardiac hypertrophy, which contributes to heart failure. The authors report a novel paracrine mechanism between cardiac fibroblasts (CF)s and cardiomyocytes whereby Ang II induces pathological cardiac hypertrophy. In cultured rat CFs, Ang II treatment enhanced exosome release via the activation of Ang II receptor types 1 (AT1R) and 2 (AT2R), whereas lipopolysaccharide, insulin, endothelin (ET)-1, transforming growth factor beta (TGFbeta)1 or hydrogen peroxide did not. PMID:26497614 ANG (1-7) acts primarily via the G protein-coupled receptor MAS1, and forms ANG (1-5), which signals via MRGPRD. ANG (1-7) can also act via the AGTR2 receptor but with much lower affinity than ANG II. PMID:32333398 Ang A has the same affinity to the AT1 receptor as Ang II, but a higher affinity to the AT2 receptor. PMID:17138938 ANG (1-7) acts primarily via the G protein-coupled receptor MAS1, and forms ANG (1-5), which signals via MRGPRD. ANG (1-7) can also act via the AGTR2 receptor but with much lower affinity than ANG II. PMID:32333398 The study investigated whether a vasodepressor effect of Ang-(1-7) could be unmasked acutely in conscious spontaneously hypertensive rats (SHR) against a background of angiotensin II type 1 (AT1) receptor blockade. Mean arterial pressure (MAP) and heart rate were measured over a 5-day protocol in various groups of rats randomized to receive the following drug combinations: saline, AT1 receptor (AT1R) antagonist candesartan (0.01 or 0.1 mg/kg IV) alone, Ang-(1-7) (5 pmol/min) alone, candesartan plus Ang-(1-7), and candesartan plus Ang-(1-7) and angiotensin II type 2 (AT2) receptor (AT2R) antagonist PD123319 (50 microg/kg per minute). In Wistar-Kyoto (WKY) rats, saline, Ang-(1-7), or candesartan alone caused no significant alteration in MAP, whereas Ang-(1-7) coadministered with candesartan caused a marked, sustained reduction in MAP. A similar unmasking of a vasodepressor response to Ang-(1-7) during AT1R blockade was observed in SHR. Moreover, the AT(2)R antagonist PD123319 markedly attenuated the enhanced depressor response evoked by the Ang-(1-7)/candesartan combination in SHR and WKY rats. In separate experiments, the bradykinin type 2 receptor antagonist HOE 140 (100 microg/kg IV) or the NO synthase inhibitor Nomega-nitro-L-arginine methyl ester (1 mg/kg IV) abolished the depressor effect of Ang-(1-7) in the presence of candesartan. Collectively, these results suggest that Ang-(1-7) evoked a depressor response during AT1R blockade via activation of AT2R, which involves the bradykinin-NO cascade. PMID:15767466 Systemic delivery of angiotensin-(1-9) significantly decreased cell death and improved left ventricular recovery after in vivo myocardial infarction. In vitro, angiotensin-(1-9) decreased cell death in isolated neonatal rat ventricular cardiomyocytes subjected to simulated ischemia/reperfusion. The cardioprotective effects of angiotensin-(1-9) were blocked by PD123319 (AT2R antagonist) and Akt inhibitor but not by A779 (Mas antagonist). Angiotensin-(1-9) limits reperfusion-induced cell death by an AT2R- and Akt-dependent mechanism. PMID:30048754 </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re67"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:25014541" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> <rdf:Description rdf:about="#re81"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:17630322" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:17138938" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> <rdf:Description rdf:about="#re138"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:15767466" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:10116" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> <rdf:Description rdf:about="#re139"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:30048754" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:10116" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa27"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa77" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa27_in_0" /><qual:input qual:qualitativeSpecies="sa32" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa27_in_1" /><qual:input qual:qualitativeSpecies="sa159" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa27_in_2" /><qual:input qual:qualitativeSpecies="sa24" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa27_in_3" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa27" qual:transitionEffect="assignmentLevel" qual:id="tr_sa27_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><or /><apply><and /><apply><eq /><ci>sa77</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa32</ci><cn type="integer">1</cn></apply></apply><apply><and /><apply><eq /><ci>sa77</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa159</ci><cn type="integer">1</cn></apply></apply><apply><and /><apply><eq /><ci>sa77</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa24</ci><cn type="integer">1</cn></apply></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body>Angiotensin-(1-5) [Ang-(1-5)], which is a metabolite of Angiotensin-(1-7) [Ang-(1-7)] catalyzed by angiotensin-converting enzyme (ACE), is a pentapeptide of the renin-angiotensin system (RAS). It has been reported that Ang-(1-7) and Ang-(1-9) stimulate the secretion of atrial natriuretic peptide (ANP) via Mas receptor (Mas R) and Ang II type 2 receptor (AT2R), respectively. The effect of Ang-(1-5) on ANP secretion was investigated using isolated perfused beating rat atria. Ang-(1-5) stimulated high pacing frequency-induced ANP secretion in a dose-dependent manner. Ang-(1-5)-induced ANP secretion was attenuated by the pretreatment with an antagonist of Mas R (A-779) but not by an antagonist of AT1R (losartan) or AT2R (PD123,319). PMID:27660028 In support of this hypothesis we show that the non-peptide MAS agonist AR234960 increases both mRNA and protein levels of CTGF via ERK1/2 signaling in HEK293-MAS cells and adult human cardiac fibroblasts. PMID:29287092 ANG-(1-7) itself acts on the receptor MAS to influence a range of mechanisms in the heart, kidney, brain, and other tissues. PMID:29351514 Angiotensin (Ang)-(1-7) has cardiovascular protective effects and is the opponent of the often detrimental Ang II within the renin-angiotensin system. The study aimed to identify a second messenger stimulated by Ang-(1-7) allowing confirmation as well as discovery of the heptapeptide's receptors. Ang-(1-7) elevates cAMP concentration in primary cells, such as endothelial or mesangial cells. Using cAMP as readout in receptor-transfected human embryonic kidney (HEK293) cells, the study provided pharmacological proof that Mas is a functional receptor for Ang-(1-7). Moreover, the authors identified the G-protein-coupled receptor MrgD as a second receptor for Ang-(1-7). PMID:27217404 </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re42"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:27660028" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:10116" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> <rdf:Description rdf:about="#re127"> <bqmodel:is> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:29287092" /> </rdf:Bag> </bqmodel:is> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> <rdf:Description rdf:about="#re140"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:27217404" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa29"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa200" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa29_in_0" /><qual:input qual:qualitativeSpecies="sa37" qual:transitionEffect="none" qual:sign="negative" qual:id="tr_sa29_in_1" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa29" qual:transitionEffect="assignmentLevel" qual:id="tr_sa29_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><and /><apply><eq /><ci>sa200</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa37</ci><cn type="integer">0</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body>Addition of estradiol (E2) to HUVEC cells induces a concentration-dependent increase of ACE1 and ACE2 mRNA expression and ACE1, but not ACE2, protein levels. ACE1 and ACE2 enzymatic activities are also induced with E2. These effects were mediated through estrogen receptor alpha activation, since ER antagonists ICI 182780 and MPP completely abolishes the effect of E2. PMID:26562171 Calcitriol inhibits ACE and AT1R expression, and induces ACE2 expression in LPS-treated rat PMVECs. PMID:28944831 </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re197"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:26562171" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:28944831" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:10116" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa30"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa168" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa30_in_0" /><qual:input qual:qualitativeSpecies="sa169" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa30_in_1" /><qual:input qual:qualitativeSpecies="sa38" qual:transitionEffect="none" qual:sign="negative" qual:id="tr_sa30_in_2" /><qual:input qual:qualitativeSpecies="sa201" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa30_in_3" /><qual:input qual:qualitativeSpecies="sa165" qual:transitionEffect="none" qual:sign="negative" qual:id="tr_sa30_in_4" /><qual:input qual:qualitativeSpecies="sa54" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa30_in_5" /><qual:input qual:qualitativeSpecies="sa202" qual:transitionEffect="none" qual:sign="negative" qual:id="tr_sa30_in_6" /><qual:input qual:qualitativeSpecies="sa203" qual:transitionEffect="none" qual:sign="negative" qual:id="tr_sa30_in_7" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa30" qual:transitionEffect="assignmentLevel" qual:id="tr_sa30_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><or /><apply><and /><apply><or /><apply><eq /><ci>sa169</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa201</ci><cn type="integer">1</cn></apply></apply><apply><eq /><ci>sa168</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa38</ci><cn type="integer">0</cn></apply></apply><apply><eq /><ci>sa165</ci><cn type="integer">0</cn></apply><apply><and /><apply><eq /><ci>sa168</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa54</ci><cn type="integer">1</cn></apply></apply><apply><and /><apply><eq /><ci>sa168</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa202</ci><cn type="integer">0</cn></apply><apply><eq /><ci>sa203</ci><cn type="integer">0</cn></apply></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body>Human bronchial epithelial cells treated with 17-beta-estradiol (E2), expressed lower levels of ACE2 mRNA compared with the vehicle-treated controls. The levels of TMPRSS2 mRNA were not affected by E2 treatment. PMID:32432918 Addition of estradiol (E2) to HUVEC cells induces a concentration-dependent increase of ACE1 and ACE2 mRNA expression and ACE1, but not ACE2, protein levels. ACE1 and ACE2 enzymatic activities are also induced with E2. These effects were mediated through estrogen receptor alpha activation, since ER antagonists ICI 182780 and MPP completely abolishes the effect of E2. PMID:26562171 Calcitriol inhibits ACE and AT1R expression, and induces ACE2 expression in LPS-treated rat PMVECs. PMID:28944831 Recombinant SARS-CoV spike protein downregulates ACE2 expression and thereby promotes lung injury. PMID:19864379 By using quantitative translatome and proteomics the authors found that the protein level of ACE2 is mildly reduced after infection. PMID:32408336 We found age-dependent ACE2 gene expression in nasal epithelium. ACE2 gene expression was lowest (mean log2 counts per million, 2.40; 95% CI, 2.07-2.72) in younger children (n = 45) and increased with age, with mean log2 counts per million of 2.77 (95% CI, 2.64-2.90) for older children (n = 185), 3.02 (95% CI, 2.78-3.26) for young adults (n = 46), and 3.09 (95% CI, 2.83-3.35) for adults (n = 29). PMID:32432657 The present study explored the signaling mechanism by which ACE2 is regulated under hypertensive conditions. Real-time PCR and immunohistochemistry showed that ACE2 mRNA and protein expression levels were high, whereas ACE expression levels were moderate in both normal kidney and heart. In contrast, patients with hypertension showed marked ACE up-regulation and ACE2 down-regulation in both hypertensive cardiopathy and, particularly, hypertensive nephropathy. PMID:18403595 ACE2 and ACE mRNA levels were measured by real-time PCR in laser microdissected renal biopsies from 13 diabetic and 8 control patients. ACE2 mRNA was significantly reduced by more than half in both the glomeruli and proximal tubules of the diabetic patients compared to controls, but ACE mRNA was increased in both compartments. PMID:19034303 </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re153"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:32432918" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:19864379" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:uniprot:P59594" /> </rdf:Bag> </bqbiol:isEncodedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:26562171" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:28944831" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:10116" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> <rdf:Description rdf:about="#re168"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:32408336" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> <rdf:Description rdf:about="#re189"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:32432657" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> <rdf:Description rdf:about="#re200"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:18403595" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:19034303" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa32"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa24" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa32_in_0" /><qual:input qual:qualitativeSpecies="sa100" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa32_in_1" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa32" qual:transitionEffect="assignmentLevel" qual:id="tr_sa32_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><and /><apply><eq /><ci>sa24</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa100</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body>Incubation of Ang1-9 with ACE in vitro generated Ang1-7 and Ang1-5, apparently by sequential cleavage of C-terminal dipeptides. PMID:10969042 </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#CDMT00034"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:10969042" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa34"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa134" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa34_in_0" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa34" qual:transitionEffect="assignmentLevel" qual:id="tr_sa34_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><eq /><ci>sa134</ci><cn type="integer">1</cn></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body>The effects of ethynylestradiol (EE) on liver AOG mRNA and plasma AOG has been tested in intact male and ovariectomized female rats, as well as in hypophysectomized male rats. EE stimulated both variables to a comparable extent and in a dose-dependent manner. However, its effect on plasma AOG was significantly higher in female than in male rats. PMID:8351287 </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re167"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:8351287" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:10116" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa40"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa132" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa40_in_0" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa40" qual:transitionEffect="assignmentLevel" qual:id="tr_sa40_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><eq /><ci>sa132</ci><cn type="integer">1</cn></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body>The expression level of TMPRSS2 increased 6-fold in androgen stimulated LNCaP cells. PMID:10485450 </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re112"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:10485450" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa49"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa24" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa49_in_0" /><qual:input qual:qualitativeSpecies="sa51" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa49_in_1" /><qual:input qual:qualitativeSpecies="sa30" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa49_in_2" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa49" qual:transitionEffect="assignmentLevel" qual:id="tr_sa49_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><or /><apply><eq /><ci>sa24</ci><cn type="integer">1</cn></apply><apply><and /><apply><eq /><ci>sa51</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa30</ci><cn type="integer">1</cn></apply></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body>Ang-(1–7) can be processed to alamandine in the isolated rat heart. PMID:23446738 Using mass spectrometry the authors identified alamandine as a product of the catalytic hydrolysis of the octapeptide Ala1-AngII (angiotensin A) by human ACE2. They demonstrate that alamandine can be formed in the rat heart after Ang-(1–7) perfusion with the use of selected reaction monitoring-mass spectrometry. This indicates that the cardiac tissue contains all necessary components to promote the decarboxylation of the Ang-(1–7) N-terminal aspartate amino acid residue. The sequence of alamandine is very similar to Ang-(1–7), differing only by the presence of an alanine residue in place of an aspartate residue in the amino terminus. PMID:23446738 </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re43"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:23446738" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:10116" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> <rdf:Description rdf:about="#re46"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:23446738" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa50"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa94" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa50_in_0" /><qual:input qual:qualitativeSpecies="sa49" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa50_in_1" /><qual:input qual:qualitativeSpecies="sa24" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa50_in_2" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa50" qual:transitionEffect="assignmentLevel" qual:id="tr_sa50_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><or /><apply><and /><apply><eq /><ci>sa94</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa49</ci><cn type="integer">1</cn></apply></apply><apply><and /><apply><eq /><ci>sa94</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa24</ci><cn type="integer">1</cn></apply></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body>To further address the role of MrgD in the alamandine effects, binding and functional studies in human MrgD-transfected cells were performed. Fluorescent-labeled alamandine specifically binds to MrgD-stably CHO cells transfected with human proteins. PMID:23446738 Angiotensin (Ang)-(1-7) has cardiovascular protective effects and is the opponent of the often detrimental Ang II within the renin-angiotensin system. The study aimed to identify a second messenger stimulated by Ang-(1-7) allowing confirmation as well as discovery of the heptapeptide's receptors. Ang-(1-7) elevates cAMP concentration in primary cells, such as endothelial or mesangial cells. Using cAMP as readout in receptor-transfected human embryonic kidney (HEK293) cells, the study provided pharmacological proof that Mas is a functional receptor for Ang-(1-7). Moreover, the authors identified the G-protein-coupled receptor MrgD as a second receptor for Ang-(1-7). PMID:27217404 </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re90"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:23446738" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> <rdf:Description rdf:about="#re141"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:27217404" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa51"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa23" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa51_in_0" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa51" qual:transitionEffect="assignmentLevel" qual:id="tr_sa51_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><eq /><ci>sa23</ci><cn type="integer">1</cn></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body>Chromatographic purification and structural analysis by matrix-assisted laser desorption/ionisation time-of-flight/time-of-flight (MALDI-TOF/TOF) revealed an angiotensin octapeptide with the sequence Ala-Arg-Val-Tyr-Ile-His-Pro-Phe, which differs from Ang II in Ala1 instead of Asp1. Des[Asp1]-[Ala1]-Ang II, in the following named Angiotensin A (Ang A), is most likely generated enzymatically. In the presence of mononuclear leukocytes, Ang II is converted to Ang A by decarboxylation of Asp1. PMID:17138938 </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re45"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:17138938" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa56"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa25" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa56_in_0" /><qual:input qual:qualitativeSpecies="sa27" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa56_in_1" /><qual:input qual:qualitativeSpecies="sa156" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa56_in_2" /><qual:input qual:qualitativeSpecies="sa50" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa56_in_3" /><qual:input qual:qualitativeSpecies="sa102" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa56_in_4" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa56" qual:transitionEffect="assignmentLevel" qual:id="tr_sa56_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><or /><apply><eq /><ci>sa25</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa27</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa156</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa50</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa102</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body>AT2R is involved in vasodilatation and regulates pancreas development. PMID:30404071 Mas-deficient aortas lose their Ang-(1-7)-induced relaxation response. PMID:12829792 AngIV-binding at AT4 sites causes a vasodilatory effect probably via endothelial cell release of NO. Originally identified as endothelium-derived relaxing factor, NO is released by vascular endothelial cells and smooth muscle cells. NO release leads to an increase in cGMP production and vasodilation. PMID:9493859 As previously reported for angiotensin (1-7), alamandine produces endothelial-dependent vasorelaxation in aortic rings from FVB/N mice. Similar data were obtained in aortic rings from Wistar rats. D-Pro7-Ang-(1–7) completely blocked the vasorelaxation produced by alamandine in mice aortic rings. The data reveal that its actions are independent of the known vasodilator receptors of the RAS, Mas, and angiotensin II type 2 receptor. The authors demonstrate that alamandine acts through the Mas-related G-protein-coupled receptor, member D. PMID:23446738 ANG2 interaction with AT1R leads to vasoconstriction, cell growth, inflammation, fibrosis and oxidative stress. PMID:30404071 </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re77"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:30404071" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:40674" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> <rdf:Description rdf:about="#re142"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:12829792" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:10090" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> <rdf:Description rdf:about="#re145"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:9493859" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:10116" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> <rdf:Description rdf:about="#re146"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:23446738" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:10090" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> <rdf:Description rdf:about="#re183"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:30404071" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:40674" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa61"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa50" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa61_in_0" /><qual:input qual:qualitativeSpecies="sa27" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa61_in_1" /><qual:input qual:qualitativeSpecies="sa156" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa61_in_2" /><qual:input qual:qualitativeSpecies="sa102" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa61_in_3" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa61" qual:transitionEffect="assignmentLevel" qual:id="tr_sa61_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><or /><apply><eq /><ci>sa50</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa27</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa156</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa102</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body>The study evaluated the effects of angiotensin-(1-7) (Ang-(1-7)) and the novel renin-angiotensin system (RAS) peptide, alamandine, on resting (M0), proinflammatory M(LPS+IFN-gamma), and anti-inflammatory M(IL-4) macrophage phenotypes in vitro, as well as on specific immune cell populations and macrophage subsets into the pleural cavity of LPS-induced pleurisy in mice. The results showed that Ang-(1-7) and alamandine, through Mas and MrgD receptors, respectively, do not affect M0 macrophages but reduce the proinflammatory TNF-alpha, CCL2, and IL-1beta transcript expression levels in LPS+IFN-gamma-stimulated macrophages. PMID:30918468 The study evaluated the effects of angiotensin-(1-7) (Ang-(1-7)) and the novel renin-angiotensin system (RAS) peptide, alamandine, on resting (M0), proinflammatory M(LPS+IFN-gamma), and anti-inflammatory M(IL-4) macrophage phenotypes in vitro, as well as on specific immune cell populations and macrophage subsets into the pleural cavity of LPS-induced pleurisy in mice. The results showed that Ang-(1-7) and alamandine, through Mas and MrgD receptors, respectively, do not affect M0 macrophages but reduce the proinflammatory TNF-alpha, CCL2, and IL-1beta transcript expression levels in LPS+IFN-gamma-stimulated macrophages. PMID:30918468 Angiotensin IV protects cardiac reperfusion injury by inhibiting apoptosis and inflammation via AT4R in rats. PMID:27038740 ANG2 interaction with AT1R leads to vasoconstriction, cell growth, inflammation, fibrosis and oxidative stress. PMID:30404071 </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re74"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:30918468" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:10090" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> <rdf:Description rdf:about="#re75"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:30918468" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:10090" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> <rdf:Description rdf:about="#re144"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:27038740" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:10116" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> <rdf:Description rdf:about="#re181"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:30404071" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:40674" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa62"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa23" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa62_in_0" /><qual:input qual:qualitativeSpecies="sa64" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa62_in_1" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa62" qual:transitionEffect="assignmentLevel" qual:id="tr_sa62_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><and /><apply><eq /><ci>sa23</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa64</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body>Mice received Ang II intracerebroventricularly in the presence or absence of the aminopeptidase A (APA) inhibitor, EC33 (3-amino-4-thio-butyl sulfonate) or of the aminopeptidase N (APN) inhibitor, EC27 (2-amino-pentan-1,5-dithiol). Ang II and Ang III levels were evaluated from hypothalamus homogenates by HPLC. EC33 increased the half-life of Ang II 2.6-fold and completely blocked the formation of Ang III, whereas EC27 increased the half-life of Ang III 2.3-fold. These results demonstrate that APA and APN are involved in vivo in the metabolism of brain Ang II and Ang III, respectively. PMID:8876246 </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re61"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:8876246" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:10090" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa63"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa62" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa63_in_0" /><qual:input qual:qualitativeSpecies="sa65" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa63_in_1" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa63" qual:transitionEffect="assignmentLevel" qual:id="tr_sa63_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><and /><apply><eq /><ci>sa62</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa65</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body>Mice received Ang II intracerebroventricularly in the presence or absence of the aminopeptidase A (APA) inhibitor, EC33 (3-amino-4-thio-butyl sulfonate) or of the aminopeptidase N (APN) inhibitor, EC27 (2-amino-pentan-1,5-dithiol). Ang II and Ang III levels were evaluated from hypothalamus homogenates by HPLC. EC33 increased the half-life of Ang II 2.6-fold and completely blocked the formation of Ang III, whereas EC27 increased the half-life of Ang III 2.3-fold. These results demonstrate that APA and APN are involved in vivo in the metabolism of brain Ang II and Ang III, respectively. PMID:8876246 </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re62"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:8876246" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:10090" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa64"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa162" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa64_in_0" /><qual:input qual:qualitativeSpecies="sa161" qual:transitionEffect="none" qual:sign="negative" qual:id="tr_sa64_in_1" /><qual:input qual:qualitativeSpecies="sa193" qual:transitionEffect="none" qual:sign="negative" qual:id="tr_sa64_in_2" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa64" qual:transitionEffect="assignmentLevel" qual:id="tr_sa64_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><or /><apply><and /><apply><eq /><ci>sa162</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa161</ci><cn type="integer">0</cn></apply></apply><apply><and /><apply><eq /><ci>sa162</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa193</ci><cn type="integer">0</cn></apply></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body>We demonstrated here the antihypertensive effects of RB150, a prodrug of the specific and selective aminopeptidase A inhibitor, EC33, in spontaneously hypertensive rats, a model of human essential hypertension. PMID:22710644 Serum peptidases, such as angiotensin-converting enzyme (ACE), angiotensin-converting enzyme-2 (ACE2), neutral endopeptidase (NEP), aminopeptidase N (APN), and aminopeptidase A (APA), are important elements of the renin-angiotensin system (RAS). Dysregulation of these enzymes has been associated with hypertension and cardiovascular risk. In the present study, serum activities of RAS peptidases were analyzed to evaluate the existence of sexual differences, with a possible different pattern in pre- and post-andropausal/post-menopausal participants. Significantly lower serum APA activity was observed in men with respect to women; no sex differences were detected for ACE, ACE2, NEP, or APN. PMID:28174624 </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re128"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:22710644" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:10116" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> <rdf:Description rdf:about="#re191"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:28174624" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa71"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa37" qual:transitionEffect="none" qual:sign="negative" qual:id="tr_sa71_in_0" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa71" qual:transitionEffect="assignmentLevel" qual:id="tr_sa71_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><eq /><ci>sa37</ci><cn type="integer">0</cn></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body>In wild-type mice, inhibition of 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] synthesis also led to an increase in renin expression, whereas 1,25(OH)(2)D(3) injection led to renin suppression. PMID:12122115 </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re21"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:12122115" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:10090" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa73"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa30" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa73_in_0" /><qual:input qual:qualitativeSpecies="sa43" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa73_in_1" /><qual:input qual:qualitativeSpecies="sa167" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa73_in_2" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa73" qual:transitionEffect="assignmentLevel" qual:id="tr_sa73_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><and /><apply><or /><apply><eq /><ci>sa43</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa167</ci><cn type="integer">1</cn></apply></apply><apply><eq /><ci>sa30</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body>ACE2, in particular its catalytic ectodomain, can be shed from cells into the circulation as soluble ACE2, an action mediated by the metalloprotease ADAM17, an activator of Notch pathway. PMID:32333398 ADAM17, the ACE2 sheddase, requires arginine and lysine residues within ACE2 amino acids 652 to 659 for receptor cleavage and competes with TMPRSS2 for ACE2 processing. PMID:24227843 Angiotensin II type 1 receptors promote ADAM17-mediated ACE2 shedding in the brain of hypertensive patients, leading to a loss in compensatory activity during neurogenic hypertension. PMID:28512108 </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re69"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:24227843" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:32333398" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:28512108" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa77"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa195" qual:transitionEffect="none" qual:sign="negative" qual:id="tr_sa77_in_0" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa77" qual:transitionEffect="assignmentLevel" qual:id="tr_sa77_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><eq /><ci>sa195</ci><cn type="integer">0</cn></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body>The aim of the study was to investigate whether aldosterone stimulation can modulate the intracellular RAS of immortalized human MCs by evaluating ANG-converting enzyme (ACE)/ANG II/ANG II receptor type 1 (AT1) and ANG-converting enzyme 2 (ACE2)/ANG (1-7)/MAS receptor axes. Aldosterone treatment decreased the protein expression of MAS receptor, but did not alter the expression or the catalytic activity of ACE2 and ANG (1-7) levels. Spironolactone modulated the localization of ANG II and AT1 receptor and decreased ANG (1-7) and MAS receptor levels. PMID:31165585 </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re194"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:31165585" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa95"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa165" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa95_in_0" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa95" qual:transitionEffect="assignmentLevel" qual:id="tr_sa95_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><eq /><ci>sa165</ci><cn type="integer">1</cn></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body>The Angiotensin II level in the plasma sample from 2019-nCoV infected patients was markedly elevated and linearly associated to viral load and lung injury. PMID:32048163 </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re103"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:32048163" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa96"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa95" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa96_in_0" /><qual:input qual:qualitativeSpecies="sa73" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa96_in_1" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa96" qual:transitionEffect="assignmentLevel" qual:id="tr_sa96_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><and /><apply><eq /><ci>sa95</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa73</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body>Soluble ACE2 is the main enzyme converting Ang II into Ang-(1–7) in human cerebrospinal fluid. PMID:28512108 </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re91"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:28512108" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa98"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa30" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa98_in_0" /><qual:input qual:qualitativeSpecies="sa44" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa98_in_1" /><qual:input qual:qualitativeSpecies="sa54" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa98_in_2" /><qual:input qual:qualitativeSpecies="sa202" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa98_in_3" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa98" qual:transitionEffect="assignmentLevel" qual:id="tr_sa98_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><or /><apply><and /><apply><eq /><ci>sa30</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa44</ci><cn type="integer">1</cn></apply></apply><apply><and /><apply><or /><apply><eq /><ci>sa54</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa202</ci><cn type="integer">1</cn></apply></apply><apply><eq /><ci>sa30</ci><cn type="integer">1</cn></apply></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body>Male rats showed higher cardiac ACE and ACE2 activity as well as hypertrophy compared to female rats. PMID:26171856 ACE and ACE2 activity were significantly higher in male compared to female spontaneously hypertensive rats. PMID:26010093 In women, significantly higher ACE2 serum activity was observed in older women compared to younger women. PMID:28174624 Serum ACE2 activity was the lowest in the healthy group and significantly increased in hypertensive patients, and further increased when hypertension was accompanied by heart failure with reduced ejection fraction, representing progression of cardiovascular disease toward systolic dysfunction. PMID:27965422 </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re93"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:26171856" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:10116" /> </rdf:Bag> </bqbiol:isEncodedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:26010093" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> <rdf:Description rdf:about="#re190"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:28174624" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:27965422" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa100"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa28" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa100_in_0" /><qual:input qual:qualitativeSpecies="sa54" qual:transitionEffect="none" qual:sign="negative" qual:id="tr_sa100_in_1" /><qual:input qual:qualitativeSpecies="sa44" qual:transitionEffect="none" qual:sign="negative" qual:id="tr_sa100_in_2" /><qual:input qual:qualitativeSpecies="sa195" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa100_in_3" /><qual:input qual:qualitativeSpecies="sa202" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa100_in_4" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa100" qual:transitionEffect="assignmentLevel" qual:id="tr_sa100_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><or /><apply><and /><apply><eq /><ci>sa28</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa54</ci><cn type="integer">0</cn></apply><apply><eq /><ci>sa44</ci><cn type="integer">0</cn></apply></apply><apply><and /><apply><eq /><ci>sa28</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa195</ci><cn type="integer">1</cn></apply></apply><apply><and /><apply><eq /><ci>sa28</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa202</ci><cn type="integer">1</cn></apply></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body>Significantly lower APA and ACE serum activity were observed in older men compared to older women. Significantly lower ACE serum activity was detected in older men compared to younger men. PMID:28174624 Renal cortical ACE activity was significantly higher in female than in male WKY rats. ACE2 activity did not differ significantly in male and female WKY rats in the renal cortex. PMID:23547034 The aim of the study was to investigate whether aldosterone stimulation can modulate the intracellular RAS of immortalized human MCs by evaluating ANG-converting enzyme (ACE)/ANG II/ANG II receptor type 1 (AT1) and ANG-converting enzyme 2 (ACE2)/ANG (1-7)/MAS receptor axes. High doses of aldosterone increase ACE activity. The effect of aldosterone on the catalytic activity of ACE was completely abolished with the pretreatment of SPI suggesting that the aldosterone-induced cell injuries through ANG II release were attenuated. PMID:31165585 The present study explored the signaling mechanism by which ACE2 is regulated under hypertensive conditions. Real-time PCR and immunohistochemistry showed that ACE2 mRNA and protein expression levels were high, whereas ACE expression levels were moderate in both normal kidney and heart. In contrast, patients with hypertension showed marked ACE up-regulation and ACE2 down-regulation in both hypertensive cardiopathy and, particularly, hypertensive nephropathy. PMID:18403595 </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re186"> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:28174624" /> </rdf:Bag> </bqbiol:isDescribedBy> </rdf:Description> <rdf:Description rdf:about="#re193"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:31165585" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> <rdf:Description rdf:about="#re201"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:18403595" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa102"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa26" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa102_in_0" /><qual:input qual:qualitativeSpecies="sa23" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa102_in_1" /><qual:input qual:qualitativeSpecies="sa63" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa102_in_2" /><qual:input qual:qualitativeSpecies="sa51" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa102_in_3" /><qual:input qual:qualitativeSpecies="sa69" qual:transitionEffect="none" qual:sign="negative" qual:id="tr_sa102_in_4" /><qual:input qual:qualitativeSpecies="sa24" qual:transitionEffect="none" qual:sign="negative" qual:id="tr_sa102_in_5" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa102" qual:transitionEffect="assignmentLevel" qual:id="tr_sa102_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><or /><apply><and /><apply><or /><apply><eq /><ci>sa23</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa63</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa51</ci><cn type="integer">1</cn></apply></apply><apply><eq /><ci>sa26</ci><cn type="integer">1</cn></apply></apply><apply><and /><apply><eq /><ci>sa26</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa69</ci><cn type="integer">0</cn></apply></apply><apply><and /><apply><eq /><ci>sa26</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa24</ci><cn type="integer">0</cn></apply></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body>Angiotensin II (ANGII) signaling, mediated via angiotensin II receptor type 1 (AGTR1) or type 2 (AGTR2), controls tissue remodeling in fibrosis, but the relevance of AGTR2 remains elusive. PMID:17630322 Chronic activation of the myocardial renin angiotensin system (RAS) elevates the local level of angiotensin II (Ang II) thereby inducing pathological cardiac hypertrophy, which contributes to heart failure. The authors report a novel paracrine mechanism between cardiac fibroblasts (CF)s and cardiomyocytes whereby Ang II induces pathological cardiac hypertrophy in rats. In cultured CFs, Ang II treatment enhanced exosome release via the activation of Ang II receptor types 1 (AT1R) and 2 (AT2R), whereas lipopolysaccharide, insulin, endothelin (ET)-1, transforming growth factor beta (TGFbeta)1 or hydrogen peroxide did not. PMID:26497614 Both, ANG II and ANG IV act primarily via the angiotensin II receptor type 1 (AGTR1). PMID:32333398 Ang A has the same affinity to the AT1 receptor as Ang II, but a higher affinity to the AT2 receptor. PMID:17138938 Native Xenopus lung preparations were used for Ussing chamber recordings and apically applied ANGII (10μM) induced a significant increase of short-circuit current (ISC: 8±2%, n=13). Pre-incubation with losartan (LOS), an antagonist of ATR1 prevented the effect of ANGII on ISC. PMID:24530803 Angiotensin (1-7) does not interact directly with MAS1, but can potently antagonize signaling from the AT1 receptor. PMID:29928987 </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re96"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:26497614" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:10116" /> </rdf:Bag> </bqbiol:isEncodedBy> <bqmodel:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:17630322" /> </rdf:Bag> </bqmodel:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:32333398" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:17138938" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> <rdf:Description rdf:about="#re135"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:24530803" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:8355" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> <rdf:Description rdf:about="#re136"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:29928987" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa138"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa121" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa138_in_0" /><qual:input qual:qualitativeSpecies="sa39" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa138_in_1" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa138" qual:transitionEffect="assignmentLevel" qual:id="tr_sa138_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><and /><apply><eq /><ci>sa121</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa39</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body>The metabolism of Ang-(1-12) in renal cortical membranes also revealed the formation of Ang I; however, the main products were Ang-(1-7) and Ang-(1-4) at 129 and 310 fmol/mg/min protein (n=4), respectively. Neprilysin inhibition abolished these products and substantially reduced the overall metabolism of Ang-(1-12). Incubation of Ang-(1-12) with either human or mouse neprilysin revealed identical products. PMID:22490446 </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re114"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:22490446" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:10116" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa140"><qual:listOfInputs><qual:input qual:qualitativeSpecies="csa9" qual:transitionEffect="none" qual:sign="negative" qual:id="tr_sa140_in_0" /><qual:input qual:qualitativeSpecies="sa23" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa140_in_1" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa140" qual:transitionEffect="assignmentLevel" qual:id="tr_sa140_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><and /><apply><eq /><ci>sa23</ci><cn type="integer">1</cn></apply><apply><eq /><ci>csa9</ci><cn type="integer">0</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body>The G-protein-coupled receptor Mas, encoded by the Mas proto-oncogene, has been identified as an endogenous receptor for the heptapeptide angiotensin-(1-7); however, the receptor is also suggested to be involved in actions of angiotensin II. The study tested whether this could be mediated indirectly through an interaction with the angiotensin II type 1 receptor, AT1. In transfected mammalian cells, Mas was not activated by angiotensin II; however, AT1 receptor-mediated, angiotensin II-induced production of inositol phosphates and mobilization of intracellular Ca2+ was diminished by 50% after coexpression of Mas, despite a concomitant increase in angiotensin II binding capacity. Mas and the AT1 receptor formed a constitutive hetero-oligomeric complex that was unaffected by the presence of agonists or antagonists of the 2 receptors. In vivo, Mas acts as an antagonist of the AT1 receptor; mice lacking the Mas gene show enhanced angiotensin II-mediated vasoconstriction in mesenteric microvessels. These results demonstrate that Mas can hetero-oligomerize with the AT1 receptor and by so doing inhibit the actions of angiotensin II. PMID:15809376 </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re116"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:15809376" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa146"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa29" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa146_in_0" /><qual:input qual:qualitativeSpecies="sa66" qual:transitionEffect="none" qual:sign="negative" qual:id="tr_sa146_in_1" /><qual:input qual:qualitativeSpecies="sa192" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa146_in_2" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa146" qual:transitionEffect="assignmentLevel" qual:id="tr_sa146_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><or /><apply><and /><apply><eq /><ci>sa29</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa66</ci><cn type="integer">0</cn></apply></apply><apply><and /><apply><eq /><ci>sa29</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa192</ci><cn type="integer">1</cn></apply></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body>We studied the efficacy of the ACE inhibitor lisinopril in treating overt proteinuria in comparison with the NSAID indomethacin, and evaluated some of the conditions that could influence this antiproteinuric effect. PMID:2550696 A non-significant trend was found in ACE activity among rs495828 genotype groups; however the polymorphism was significantly associated with ABO phenotype (p=0.007), which in turn was associated with ACE activity (p=0.029). PMID:24803075 That is, the GATC haplotype of the four poly-morphisms of the ABO gene (rs8176746, rs8176740, rs495828, rs12683493), which is prevalent among non- O blood type patients, is positively associated with ACE activity. PMID:32343152 We further replicated the association between ABO genotype/blood types and ACE activity in an independent YOH family study (428 hypertension pedigrees). PMID:20066004 Type O alleles were associated with intermediate plasma ACE activity compared to Type A1 alleles (in whom plasma ACE activity was ∼36% lower) and Type B alleles (in whom plasma ACE activity was ∼36% higher). We demonstrated heterogeneity among A alleles: A2 alleles were associated with plasma ACE activity that was very similar to the O alleles. PMID:23937567 </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re117"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:2550696" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> <rdf:Description rdf:about="#re188"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:24803075" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:32343152" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:20066004" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:23937567" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa156"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa152" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa156_in_0" /><qual:input qual:qualitativeSpecies="sa63" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa156_in_1" /><qual:input qual:qualitativeSpecies="sa160" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa156_in_2" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa156" qual:transitionEffect="assignmentLevel" qual:id="tr_sa156_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><or /><apply><and /><apply><eq /><ci>sa152</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa63</ci><cn type="integer">1</cn></apply></apply><apply><and /><apply><eq /><ci>sa152</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa160</ci><cn type="integer">1</cn></apply></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body>The authors identify the AT4 receptor, by protein purification and peptide sequencing, to be insulin-regulated aminopeptidase (IRAP). HEK 293T cells transfected with IRAP exhibit typical AT4 receptor binding characteristics. PMID:11707427 Ang-(3–7) is an angiotensin peptide that was shown to bind to AT4R, with lower affinity compared to Ang-IV, leading to important effects in the brain and kidney. PMID:30934934 </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re122"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:11707427" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> <rdf:Description rdf:about="#re151"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:30934934" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:40674" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa157"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa27" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa157_in_0" /><qual:input qual:qualitativeSpecies="sa102" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa157_in_1" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa157" qual:transitionEffect="assignmentLevel" qual:id="tr_sa157_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><or /><apply><eq /><ci>sa27</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa102</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body>ANG2 interaction with AT1R leads to vasoconstriction, cell growth, inflammation, fibrosis and oxidative stress. PMID:30404071 Co-incubation with losartan, an AT1R antagonist and Ang II, fully reversed the Ang II-induced oxidative stress in CATH.a cells, as the enhancement in NADPH oxidase activity and ROS generation was markedly attenuated. PMID:25666589 </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re160"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:20581171" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:10116" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> <rdf:Description rdf:about="#re184"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:30404071" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:40674" /> </rdf:Bag> </bqbiol:isEncodedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:25666589" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:10090" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa160"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa24" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa160_in_0" /><qual:input qual:qualitativeSpecies="sa23" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa160_in_1" /><qual:input qual:qualitativeSpecies="sa63" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa160_in_2" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa160" qual:transitionEffect="assignmentLevel" qual:id="tr_sa160_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><or /><apply><eq /><ci>sa24</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa23</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa63</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body>Ang-(3–7) is an angiotensin peptide that was shown to bind to AT4R, with lower affinity compared to Ang-IV, leading to important effects in the brain and kidney. Ang-(3–7) can be produced by cleavage of Ang-(1–7), Ang-II, or Ang-IV by aminopeptidases or carboxypeptidases. Administration of Ang (3–7) intracerebroventricularly (i. c. v.) significantly enhanced learning and behavioral activity in rats. Co-treatment withthe ARB, losartan, only affected learning ability, without altering the behavioral activity. This suggests that Ang (3–7) is an active peptide that exerts its effects through different receptors, one of which is AT1R. PMID:30934934 Ang-(3–7) is an angiotensin peptide that was shown to bind to AT4R, with lower affinity compared to Ang-IV, leading to important effects in the brain and kidney. Ang-(3–7) can be produced by cleavage of Ang-(1–7), Ang-II, or Ang-IV by aminopeptidases or carboxypeptidases. Administration of Ang (3–7) intracerebroventricularly (i. c. v.) significantly enhanced learning and behavioral activity in rats. Co-treatment withthe ARB, losartan, only affected learning ability, without altering the behavioral activity. This suggests that Ang (3–7) is an active peptide that exerts its effects through different receptors, one of which is AT1R. PMID:30934934 Ang-(3–7) is an angiotensin peptide that was shown to bind to AT4R, with lower affinity compared to Ang-IV, leading to important effects in the brain and kidney. Ang-(3–7) can be produced by cleavage of Ang-(1–7), Ang-II, or Ang-IV by aminopeptidases or carboxypeptidases. Administration of Ang (3–7) intracerebroventricularly (i. c. v.) significantly enhanced learning and behavioral activity in rats. Co-treatment withthe ARB, losartan, only affected learning ability, without altering the behavioral activity. This suggests that Ang (3–7) is an active peptide that exerts its effects through different receptors, one of which is AT1R. PMID:30934934 </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re147"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:30934934" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:40674" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> <rdf:Description rdf:about="#re148"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:30934934" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:40674" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> <rdf:Description rdf:about="#re149"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:30934934" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:40674" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa166"><qual:listOfInputs><qual:input qual:qualitativeSpecies="csa5" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa166_in_0" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa166" qual:transitionEffect="assignmentLevel" qual:id="tr_sa166_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><eq /><ci>csa5</ci><cn type="integer">1</cn></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body>Recently, ACE2 was reported as an entry receptor for SARS-CoV-2. In this study, we present the crystal structure of the C-terminal domain of SARS-CoV-2 (SARS-CoV-2-CTD) spike (S) protein in complex with human ACE2 (hACE2), which reveals a hACE2-binding mode similar overall to that observed for SARS-CoV. PMID:32275855 </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re152"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:32275855" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa171"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa27" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa171_in_0" /><qual:input qual:qualitativeSpecies="sa25" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa171_in_1" /><qual:input qual:qualitativeSpecies="sa102" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa171_in_2" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa171" qual:transitionEffect="assignmentLevel" qual:id="tr_sa171_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><or /><apply><eq /><ci>sa27</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa25</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa102</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body>MAS1 decreases fibroses in rats after angiotensin 1-7 treatment in bleomycin pre-treated rats. PMID:20581171 AGTR2 decreases fibrosis in rats after angiotensin 1-9 treatment. PMID:24463937 In vitro, ANG II was a potent inducer of procollagen production in human lung fibroblasts via activation of the type 1 receptor and, at least in part, via the autocrine action of TGF-beta. ACE inhibitors and receptor antagonists, already widely used clinically, should be assessed as potential new therapies for fibrotic lung disease. PMID:12754187 </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re159"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:20581171" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:10116" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> <rdf:Description rdf:about="#re165"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:24463937" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:10116" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> <rdf:Description rdf:about="#re182"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:12754187" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa172"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa27" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa172_in_0" /><qual:input qual:qualitativeSpecies="sa102" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa172_in_1" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa172" qual:transitionEffect="assignmentLevel" qual:id="tr_sa172_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><or /><apply><eq /><ci>sa27</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa102</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body>Ang-(1-7) inhibited thrombus formation in Mas+/+ mice. This effect was abolished in Mas-/-mice. PMID:18026570 ACE2 alternatively converts angiotensin (Ang) II into Ang-(1-7) and Ang I into Ang-(1-9). The study investigated the influence of Ang-(1-9) on stasis-induced venous thrombosis in the rat. The contribution of coagulation and fibrinolytic systems, angiotensin receptor type 1 (AT1) and MAS receptor in the mode of Ang-(1-9) action was also determined. Ang-(1-9) enhanced thrombosis development, decreased plasma concentration of tissue plasminogen activator and increased the level of its inhibitor (PAI-1). The action of Ang-(1-9) was reversed by selective antagonist of AT1 receptor, but not Ang-(1-7) antagonist. Ang-(1-9) did not bind to the AT1 receptor. Ang-(1-9) enhances venous thrombosis in the rat because of the impairment of fibrinolysis. The prothrombotic effect of Ang-(1-9) is mediated by Ang II acting via the AT1 receptor. PMID:23884911 </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re161"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:18026570" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:10090" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> <rdf:Description rdf:about="#re177"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:23884911" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:10116" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa190"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa156" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa190_in_0" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa190" qual:transitionEffect="assignmentLevel" qual:id="tr_sa190_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><eq /><ci>sa156</ci><cn type="integer">1</cn></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body>Ang IV acts via angiotensin receptor type 4 to mediate protective mechanisms in neurodegenerative diseases. PMID:32127770 </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re185"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:32127770" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:40674" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa194"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa39" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa194_in_0" /><qual:input qual:qualitativeSpecies="sa44" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa194_in_1" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa194" qual:transitionEffect="assignmentLevel" qual:id="tr_sa194_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><and /><apply><eq /><ci>sa39</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa44</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body>In contrast, younger (younger than 55 years) men had significantly higher values of NEP (MME) serum activity than younger women. PMID:28174624 </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re192"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:28174624" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa195"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa204" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa195_in_0" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa195" qual:transitionEffect="assignmentLevel" qual:id="tr_sa195_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><eq /><ci>sa204</ci><cn type="integer">1</cn></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body>The role of the angiotensin I1 (AII) receptor subtypes on steroidogenesis was studied by examining the relationship between binding inhibition potency of the AI1 receptor subtype antagonists and their ability to inhibit aldosterone production in isolated adrenal glomerulosa cells. Incubation of the cells with AI1 resulted in the characteristic dose-dependent increase in aldosterone production. AT1 receptor antagonism inhibited the AII-induced aldosterone production, whereas AT2 receptor antagonism had no significant effect. The studies show that the actions of AI1 on intracellular signalling systems and steroidogenesis in the adrenal glomerulosa cell are mediated by type 1 angiotensin II receptors. PMID:1338730 </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re198"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:1338730" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:10116" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa197"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa102" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa197_in_0" /><qual:input qual:qualitativeSpecies="sa156" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa197_in_1" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa197" qual:transitionEffect="assignmentLevel" qual:id="tr_sa197_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><or /><apply><eq /><ci>sa102</ci><cn type="integer">1</cn></apply><apply><eq /><ci>sa156</ci><cn type="integer">1</cn></apply></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body>Activation of AT1R by Ang II due to increased expression of ACE is known to play important role in vasoconstriction in the brain and impairs cognition. PMID:32127770 Genetic variants of AGTR1 (rs2638363, rs1492103, rs2675511) were independently associated with accelerated hippocampal volume loss over the four-year follow-up in the right but not left hemisphere in subjects aged 60 years or older. These AGTR1 risk alleles also predicted worse episodic memory performance but were not related to other cognitive measures. PMID:25124854 Application of an AT4 receptor agonist (Norleucinal) compensated for spatial memory deficits. PMID:10234025 The major effects of AT4R activation are thought to be in the brain where it can enhance learning and memory. PMID:30934934 </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re195"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:25124854" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:32127770" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:40674" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> <rdf:Description rdf:about="#re196"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:10234025" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:9606" /> </rdf:Bag> </bqbiol:isEncodedBy> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:30934934" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:40674" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa208"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa102" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa208_in_0" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa208" qual:transitionEffect="assignmentLevel" qual:id="tr_sa208_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><eq /><ci>sa102</ci><cn type="integer">1</cn></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body>AGTR1 inhibition rescues Sars-CoV-1 mediated pulmonary edema in Sars-CoV 1 infected mice. PMID:16007097 </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re202"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:16007097" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:10090" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition><qual:transition qual:id="tr_sa209"><qual:listOfInputs><qual:input qual:qualitativeSpecies="sa102" qual:transitionEffect="none" qual:sign="positive" qual:id="tr_sa209_in_0" /></qual:listOfInputs><qual:listOfOutputs><qual:output qual:qualitativeSpecies="sa209" qual:transitionEffect="assignmentLevel" qual:id="tr_sa209_out" /></qual:listOfOutputs><qual:listOfFunctionTerms><qual:defaultTerm qual:resultLevel="0" /><qual:functionTerm qual:resultLevel="1"><math xmlns="http://www.w3.org/1998/Math/MathML"><apply><eq /><ci>sa102</ci><cn type="integer">1</cn></apply></math></qual:functionTerm></qual:listOfFunctionTerms><notes><html xmlns="http://www.w3.org/1999/xhtml"><head><title /></head><body>Thrombin-induced platelet aggregation was dose-dependently inhibited in Agtr1(-/-) platelets compared with Agtr1(+/+) platelets, accompanied by the reduced expression and release of SDF-1alpha. PMID:19834109 </body></html></notes><annotation><rdf:RDF><rdf:Description rdf:about="#re203"> <bqbiol:isDescribedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:pubmed:19834109" /> </rdf:Bag> </bqbiol:isDescribedBy> <bqbiol:isEncodedBy> <rdf:Bag> <rdf:li rdf:resource="urn:miriam:taxonomy:10090" /> </rdf:Bag> </bqbiol:isEncodedBy> </rdf:Description> </rdf:RDF></annotation></qual:transition></qual:listOfTransitions></model></sbml>

sa26 1 sa23 0