Elastase‐2, an angiotensin II‐generating enzyme, contributes to increased angiotensin II in resistance arteries of mice with myocardial infarction
| Autor: | Maurício Serra Ribeiro, Helio Cesar Salgado, Marina T. Durand, Eduardo B. Oliveira, Christiane Becari, Rita C. Tostes, Maria Cristina O. Salgado, Marcondes A. B. Silva, Cibele M. Prado |
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| Rok vydání: | 2017 |
| Předmět: |
Male
Cardiac function curve medicine.medical_specialty Cardiac output Myocardial Infarction 030204 cardiovascular system & hematology Mice 03 medical and health sciences 0302 clinical medicine Internal medicine Renin–angiotensin system medicine Animals Myocardial infarction Ligation Mice Knockout Pharmacology Ejection fraction business.industry Angiotensin II Serine Endopeptidases Elastase medicine.disease Research Papers Coronary Vessels INFARTO DO MIOCÁRDIO Mesenteric Arteries Mice Inbred C57BL Endocrinology cardiovascular system business 030217 neurology & neurosurgery |
| Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| ISSN: | 1476-5381 0007-1188 |
| DOI: | 10.1111/bph.13755 |
| Popis: | Background and Purpose Angiotensin II (Ang II), whose generation largely depends on angiotensin-converting enzyme (ACE) activity, mediates most of the renin-angiotensin-system (RAS) effects. Elastase-2 (ELA-2), a chymotrypsin-serine protease elastase family member 2A, alternatively generates Ang II in rat arteries. Myocardial infarction (MI) leads to intense RAS activation, but mechanisms involved in Ang II-generation in resistance arteries are unknown. We hypothesized that ELA-2 contributes to vascular Ang II generation and cardiac damage in mice subjected to MI. Experimental Approach Concentration-effect curves to Ang I and Ang II were performed in mesenteric resistance arteries from male wild type (WT) and ELA-2 knockout (ELA-2KO) mice subjected to left anterior descending coronary artery ligation (MI). Key Results MI size was similar in WT and ELA-2KO mice. Ejection fraction and fractional shortening after MI similarly decreased in both strains. However, MI decreased stroke volume and cardiac output in WT, but not in ELA-2KO mice. Ang I-induced contractions increased in WT mice subjected to MI (MI-WT) compared with sham-WT mice. No differences were observed in Ang I reactivity between arteries from ELA-2KO and ELA-2KO subjected to MI (MI-ELA-2KO). Ang I contractions increased in arteries from MI-WT versus MI-ELA-2KO mice. Chymostatin attenuated Ang I-induced vascular contractions in WT mice, but did not affect Ang I responses in ELA-2KO arteries. Conclusions and Implications These results provide the first evidence that ELA-2 contributes to increased Ang II formation in resistance arteries and modulates cardiac function after MI, implicating ELA-2 as a key player in ACE-independent dysregulation of the RAS. |
| Databáze: | OpenAIRE |
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