title: Inhibition of endostatin/collagen XVIII deteriorates left ventricular remodeling and heart failure in rat myocardial infarction model.
abstract: BACKGROUND
  Although therapeutic angiogenesis is a most promising strategy for the treatment of myocardial infarction (MI), it remains unknown if and how endogenous angiogenesis inhibitors, such as endostatin, regulate angiogenesis in MI. In the present study the role of endostatin in left ventricular (LV) remodeling and heart failure was tested in a rat MI model.
  
  
  RESULTS
  When exposed to hypoxia, rat cardiomyocytes showed increased expression of endostatin. After MI induction in the rat MI model, endostatin expression was upregulated in cardiomyocytes, and serum endostatin levels were significantly elevated. Anti-endostatin antibody treatment resulted in significantly higher mortality of MI rats than controls. The MI rats with endostatin neutralization displayed adverse LV remodeling and severe heart failure compared with control MI rats. Although angiogenesis was increased, tissue remodeling and interstitial fibrosis were further exaggerated in post-MI hearts by endostatin neutralization. Furthermore, the expression and protease activity of matrix metalloproteinases -2 and -9, and of angiotensin-converting enzyme were markedly elevated by endostatin neutralization.
  
  
  CONCLUSIONS
  Neutralization of endostatin worsens the symptoms and outcomes of MI in a rat model. The results imply that endogenous endostatin/collagen XVIII may suppress aberrant LV remodeling and heart failure after MI. (Circ J 2010; 74: 109 - 119).
authors: Department of Cardiovascular Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
authors: Kazuya
authors: K
authors: Isobe
authors: Keiji
authors: K
authors: Kuba
authors: Yasuhiro
authors: Y
authors: Maejima
authors: Jun-Ichi
authors: J
authors: Suzuki
authors: Shunichiro
authors: S
authors: Kubota
authors: Mitsuaki
authors: M
authors: Isobe
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D043170:Collagen Type XVIII / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000502:physiology; D004195:Disease Models, Animal; D043169:Endostatins / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000502:physiology; D006333:Heart Failure / Q000378:metabolism / Q000503:physiopathology*; D007074:Immunoglobulin G / Q000494:pharmacology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D009203:Myocardial Infarction / Q000378:metabolism / Q000503:physiopathology*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D020257:Ventricular Remodeling / Q000502:physiology*
chemical_list: D043170:Collagen Type XVIII; D043169:Endostatins; D007074:Immunoglobulin G; D007703:Peptidyl-Dipeptidase A; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9