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

• We investigated (pro)renin receptor blockade following myocardial infarction (MI) in mice.
• (P)RR blockade after MI ameliorates infarct size and cardiac dysfunction.
• (P)RR antagonism reverses MI-induced cardiac fibrosis and hypertrophy.
• Blockade of the (pro)renin receptor is a potential therapeutic target after MI.

BackgroundThe (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 ResultsMice 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.ConclusionsThe 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.