title: (Pro)renin Receptor Blockade Ameliorates Cardiac Injury and Remodeling and Improves Function After Myocardial Infarction.
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.
  
  
  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 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.
  
  
  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.
authors.affiliation: Department of Medicine, Christchurch Heart Institute, University of Otago, Christchurch, New Zealand.
authors.forename: Leigh J
authors.initials: LJ
authors.lastname: Ellmers
authors.affiliation: Department of Medicine, Christchurch Heart Institute, University of Otago, Christchurch, New Zealand. Electronic address: miriam.rademaker@otago.ac.nz.
authors.forename: Miriam T
authors.initials: MT
authors.lastname: Rademaker
authors.affiliation: Department of Medicine, Christchurch Heart Institute, University of Otago, Christchurch, New Zealand.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Charles
authors.affiliation: Department of Medicine, Christchurch Heart Institute, University of Otago, Christchurch, New Zealand.
authors.forename: Tim G
authors.initials: TG
authors.lastname: Yandle
authors.affiliation: Department of Medicine, Christchurch Heart Institute, University of Otago, Christchurch, New Zealand.
authors.forename: A Mark
authors.initials: AM
authors.lastname: Richards
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000517:prevention & control; D005355:Fibrosis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology*; D009206:Myocardium / Q000473:pathology*; D009842:Oligopeptides / Q000494:pharmacology* / Q000627:therapeutic use; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors*; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors*; D016277:Ventricular Function, Left / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects*; D000093342:Prorenin Receptor
chemical_list: D009842:Oligopeptides; D006180:Proton-Translocating ATPases; D011956:Receptors, Cell Surface; C583530:ATP6AP2 protein, mouse; D000093342:Prorenin Receptor; C530358:handle-region peptide, mouse
keywords: (Pro)renin receptor; cardiac fibrosis; cardiac remodelling; left ventricular function; myocardial infarction