(Pro)renin Receptor Blockade Ameliorates Cardiac Injury and Remodeling and Improves Function After Myocardial Infarction

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.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 β-myosin heavy chain (β-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), β-MHC (P = .06), transforming growth factor β1 (P.01), and angiotensin-converting enzyme (P.05) expression.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.