(Pro)renin Receptor Blockade Ameliorates Cardiac Injury and Remodeling and Improves Function After Myocardial Infarction.
J Card Fail
; 22(1): 64-72, 2016 Jan.
Article
em En
| MEDLINE
| ID: mdl-26362519
ABSTRACT
BACKGROUND:
The (pro)renin receptor [(P)RR] is implicated in the pathogenesis of cardiovascular disease. We investigated the effects of (P)RR blockade after myocardial infarction (MI) in a mouse coronary-ligation model. METHODS ANDRESULTS:
Mice underwent sham control surgeries (n = 8) or induction of MI followed by 28 days' treatment with a vehicle control (n = 8) or (P)RR antagonist (n = 8). Compared with sham control subjects, MI + vehicle mice demonstrated reduced left ventricular (LV) ejection fraction (LVEF P < .001) and fractional shortening (P < .001), and increased LV end-systolic and -diastolic volumes (LVESV P < .001; LVEDV P < .001) 28 days after MI. In addition, MI decreased LV posterior wall and septal diameters (both P < .001), increased heart weight-body weight ratios (P < .05), LV collagen deposition, and cardiomyocyte diameter (both P < .001), and up-regulated collagen 1 (P < .01) and ß-myosin heavy chain (ß-MHC P < .05) mRNA. Compared with MI + vehicle mice, (P)RR antagonism after MI reduced infarct size (P < .01), improved LVEF (P < .001), fractional shortening (P < .001), and stroke volume (P < .05), and decreased LVESV (P < .001) and LVEDV (P < .001). (P)RR antagonism also reversed MI-induced transmural thinning (P < .001) and reduced LV fibrosis (P < .01), cardiomyocyte size (P < .001), and ventricular collagen 1 (P < .01), ß-MHC (P = .06), transforming growth factor ß1 (P < .01), and angiotensin-converting enzyme (P < .05) expression.CONCLUSIONS:
The present study found that (P)RR blockade after MI in mice ameliorates infarct size, cardiac fibrosis/hypertrophy, and cardiac dysfunction and identifies the receptor as a potential therapeutic target in this setting.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oligopeptídeos
/
ATPases Translocadoras de Prótons
/
Receptores de Superfície Celular
/
Remodelação Ventricular
/
Infarto do Miocárdio
/
Miocárdio
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Card Fail
Assunto da revista:
CARDIOLOGIA
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Nova Zelândia