Author Hayashidani S, Tsutsui H, Ikeuchi M, Shiomi T, Matsusaka H, Kubota T, Imanaka-Yoshida K, Itoh T, Takeshita A.
Title Targeted deletion of MMP-2 attenuates early LV rupture and late remodeling after experimental myocardial infarction.
Journal Am J Physiol Heart Circ Physiol
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.
Volume 285(3)
Pages H1229-35
Published 2003-9-1
DOI 10.1152/ajpheart.00207.2003
PII 00207.2003
PMID 12775562
MeSH Animals Blood Pressure Echocardiography Gene Deletion Heart Rupture, Post-Infarction / diagnostic imaging Heart Rupture, Post-Infarction / mortality Heart Rupture, Post-Infarction / pathology Heart Rupture, Post-Infarction / physiopathology* Heart Ventricles / pathology Heart Ventricles / physiopathology Male Matrix Metalloproteinase 2 / genetics* Mice Mice, Inbred C57BL Mice, Knockout Myocardial Infarction / diagnostic imaging Myocardial Infarction / mortality Myocardial Infarction / pathology Myocardial Infarction / physiopathology* Myocardium / pathology Survival Rate Ventricular Pressure Ventricular Remodeling / physiology*
IF 3.864
Times Cited 241
Mice RBRC00398