Inhibition of Endostatin/Collagen XVIII Deteriorates Left Ventricular Remodeling and Heart Failure in Rat Myocardial Infarction Model

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Author(s)

    • ISOBE Kazuya
    • Department of Cardiovascular Medicine, Tokyo Medical and Dental University
    • KUBA Keiji
    • Medical Research Institute, MTT Program, Tokyo Medical and Dental University
    • MAEJIMA Yasuhiro
    • Department of Cardiovascular Medicine, Tokyo Medical and Dental University
    • SUZUKI Jun-ichi
    • Department of Cardiovascular Medicine, Tokyo Medical and Dental University
    • KUBOTA Shunichiro
    • Department of Advanced Clinical Science and Therapeutics, Graduate School of Medicine, University of Tokyo
    • ISOBE Mitsuaki
    • Department of Cardiovascular Medicine, Tokyo Medical and Dental University

Abstract

<b><i>Background:</i></b> 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. <b><i>Methods and Results:</i></b> 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. <b><i>Conclusions:</i></b> 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. (<i>Circ J</i> 2010; <b>74:</b> 109 - 119)<br>

Journal

  • Circulation Journal

    Circulation Journal 74(1), 109-119, 2009-12-20

    The Japanese Circulation Society

References:  35

Cited by:  5

Codes

  • NII Article ID (NAID)
    10025941400
  • NII NACSIS-CAT ID (NCID)
    AA11591968
  • Text Lang
    ENG
  • Article Type
    Journal Article
  • ISSN
    13469843
  • Data Source
    CJP  CJPref  J-STAGE 
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