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 and Results: 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 beta-myosin heavy chain (beta-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), beta-MHC (P =.06), transforming growth factor 131 (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. (J Cardiac Fail 2016;22:64-72)