title: Effects of angiotensin II blockade on cardiomyocyte regeneration after myocardial infarction in rats.
abstract: BACKGROUND
  We studied the effects of angiotensin type 1 receptor blockade (ARB) on formation of new cardiomyocytes, neovascularization and ventricular remodelling after myocardial infarction (MI).
  
  
  METHODS
  Male Wistar rats with MI or sham-operated controls were treated with either losartan or vehicle. Bromodeoxyuridine (BrdU) was given to identify newly formed cardiac cells. Immunohistochemical analysis was used to quantify proliferative and apoptotic cardiomyocytes, vascular structures and c-Kit+ stem/progenitor cells, western blotting to evaluate gene expression, and planimetry and echocardiography to assess cardiac structure and function.
  
  
  RESULTS
  The number of BrdU+ cardiomyocytes increased similarly in the vehicle and losartan treated MI groups. The number of apoptotic or proliferating cardiomyocytes did not differ between losartan and vehicle treated rats. Losartan induced an increase in capillary and BrdU+ vascular densities in the infarct border zone. Losartan treatment completely prevented post-MI cardiac hypertrophy. In the non-infarcted myocardium the amount of all BrdU+ cells (including non-cardiomyocyte cells) was highest in the vehicle treated MI rats at week 4.
  
  
  CONCLUSIONS
  The number of newly formed cardiomyocytes increased after MI. Angiotensin II blockade neither stimulated nor prevented cardiomyocyte regeneration. ARB treatment increased vascular densities in the infarct border zone and modulated remodelling of the non-infarcted myocardium preventing effectively post-MI cardiac hypertrophy.
authors: Minerva Institute for Medical Research, Helsinki, Finland heli.segersvard@helsinki.fi.
authors: Heli
authors: H
authors: Segersvärd
authors: Minerva Institute for Medical Research, Helsinki, Finland Department of Clinical Chemistry, Helsinki University Central Hospital, Finland.
authors: Päivi
authors: P
authors: Lakkisto
authors: Minerva Institute for Medical Research, Helsinki, Finland.
authors: Hanna
authors: H
authors: Forsten
authors: Minerva Institute for Medical Research, Helsinki, Finland.
authors: Katariina
authors: K
authors: Immonen
authors: Minerva Institute for Medical Research, Helsinki, Finland.
authors: Riikka
authors: R
authors: Kosonen
authors: Minerva Institute for Medical Research, Helsinki, Finland Department of Medicine, Helsinki University Central Hospital, Finland.
authors: Eeva
authors: E
authors: Palojoki
authors: Institute of Biomedicine, Pharmacology, Biomedicum, University of Helsinki, Finland.
authors: Esko
authors: E
authors: Kankuri
authors: Institute of Biomedicine, Pharmacology, Biomedicum, University of Helsinki, Finland Department of Cardiothoracic Surgery, Helsinki University Central Hospital, Finland.
authors: Ari
authors: A
authors: Harjula
authors: Minerva Institute for Medical Research, Helsinki, Finland Department of Clinical Chemistry, Helsinki University Central Hospital, Finland.
authors: Mika
authors: M
authors: Laine
authors: Minerva Institute for Medical Research, Helsinki, Finland Department of Clinical Chemistry, Helsinki University Central Hospital, Finland.
authors: Ilkka
authors: I
authors: Tikkanen
mesh_terms: D057912:Angiotensin II Type 2 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001835:Body Weight; D001973:Bromodeoxyuridine / Q000494:pharmacology; D006332:Cardiomegaly / Q000209:etiology / Q000517:prevention & control; D019808:Losartan / Q000494:pharmacology; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000187:drug effects*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D051381:Rats; D012038:Regeneration / Q000187:drug effects; D012083:Renin / Q000097:blood; D013234:Stem Cells; D014463:Ultrasonography; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
chemical_list: D057912:Angiotensin II Type 2 Receptor Blockers; D000963:Antimetabolites; D042461:Vascular Endothelial Growth Factor A; D019009:Proto-Oncogene Proteins c-kit; D012083:Renin; D001973:Bromodeoxyuridine; D019808:Losartan
keywords: AT-receptor antagonist; Angiotensin II; cardiac remodelling; cardiomyocyte regeneration; myocardial infarction; neovascularization; rats