| Texto completo | |
| Autor(es): |
Becari, Christiane
;
Silva, Marcondes A. B.
;
Durand, Marina T.
;
Prado, Cibele M.
;
Oliveira, Eduardo B.
;
Ribeiro, Mauricio S.
;
Salgado, Helio C.
;
Salgado, Maria Cristina O.
;
Tostes, Rita C.
Número total de Autores: 9
|
| Tipo de documento: | Artigo Científico |
| Fonte: | British Journal of Pharmacology; v. 174, n. 10, p. 12-pg., 2017-05-01. |
| Resumo | |
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-2KOmice. 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. (AU) | |
| Processo FAPESP: | 13/08216-2 - CPDI - Centro de Pesquisa em Doenças Inflamatórias |
| Beneficiário: | Fernando de Queiroz Cunha |
| Modalidade de apoio: | Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs |
| Processo FAPESP: | 09/50548-7 - Caracterizacao da elastase-2, enzima formadora de angiotensina ii, em camundongos. |
| Beneficiário: | Christiane Becari |
| Modalidade de apoio: | Bolsas no Brasil - Pós-Doutorado |