Targeted deletion of MMP-2 attenuates early LV rupture and late remodeling after experimental myocardial infarction

Shunji Hayashidani, Hiroyuki Tsutsui, Masaki Ikeuchi, Tetsuya Shiomi, Hidenori Matsusaka, Toru Kubota, Kyoko Imanaka-Yoshida, Takeshi Itoh, Akira Takeshita

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256 Citations (Scopus)

Abstract

Matrix metalloproteinase-2 (MMP-2) is prominently overexpressed both after myocardial infarction (MI) and in heart failure. However, its pathophysiological significance in these conditions is still unclear. We thus examined the effects of targeted deletion of MMP-2 on post-MI left ventricular (LV) remodeling and failure. Anterior MI was produced in 10- to 12-wk-old male MMP-2 knockout (KO) and sibling wild-type (WT) mice by ligating the left coronary artery. By day 28, MI resulted in a significant increase in mortality in association with LV cavity dilatation and dysfunction. The MMP-2 KO mice had a significantly better survival rate than WT mice (56% vs. 85%, P < 0.05), despite a comparable infarct size (50 ± 3% vs. 51 ± 3%, P = not significant), heart rate, and arterial blood pressure. The KO mice had a significantly lower incidence of LV rupture (10% vs. 39%, P < 0.05), which occurred within 7 days of MI. The KO mice exerted less LV cavity dilatation and improved fractional shortening after MI by echocardiography. The LV zymographic MMP-2 level significantly increased in WT mice after coronary artery ligation; however, this was completely prevented in KO mice. In contrast, the increase in the LV zymographic MMP-9 level after MI was similar between KO and WT mice. MMP-2 activation is therefore considered to contribute to an early cardiac rupture as well as late LV remodeling after MI. The inhibition of MMP-2 activation may therefore be a potentially useful therapeutic strategy to manage post-MI hearts.

Original languageEnglish
Pages (from-to)H1229-H1235
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume285
Issue number3 54-3
DOIs
Publication statusPublished - Sep 1 2003

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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