Matrix metalloproteinase inhibition after myocardial infarction - A new approach to prevent heart failure?

被引:509
作者
Creemers, EEJM
Cleutjens, JPM
Smits, JFM
Daemen, MJAP
机构
[1] Univ Maastricht, Cardiovasc Res Inst Maastricht, Dept Pathol, NL-6200 MD Maastricht, Netherlands
[2] Univ Maastricht, Cardiovasc Res Inst Maastricht, Dept Pharmacol, NL-6200 MD Maastricht, Netherlands
关键词
myocardial infarction; therapy; matrix metalloproteinase inhibition;
D O I
10.1161/hh1501.094396
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Increased activity of matrix metalloproteinases (MMPs) has been implicated in numerous disease processes, including tumor growth and metastasis, arthritis, and periodontal disease. It is now becoming increasingly clear that extracellular matrix degradation by MMPs is also involved in the pathogenesis of cardiovascular disease, including atherosclerosis, restenosis, dilated cardiomyopathy, and myocardial infarction. Administration of synthetic MMP inhibitors in experimental animal models of these cardiovascular diseases significantly inhibits the progression of, respectively, atherosclerotic lesion formation, neointima formation, left ventricular remodeling, pump dysfunction, and infarct healing. This review focuses on the role of MMPs in cardiovascular disease, in particular myocardial infarction and the subsequent progression to heart failure. MMPs, which are present in the myocardium and capable of degrading all the matrix components of the heart, are the driving force behind myocardial matrix remodeling. The recent finding that acute pharmacological inhibition of MMPs or deficiency in MMP-9 attenuates left ventricular dilatation in the infarcted mouse heart led to the proposal that MMP inhibitors could be used as a potential therapy for patients at risk for the development of heart failure after myocardial infarction. Although these promising results encourage the design of clinical trials with MMP inhibitors, there are still several unresolved issues. This review describes the biology of MMPs and discusses new insights into the role of MMPs in several cardiovascular diseases. Attention will be paid to the central role of the plasminogen system as an important activator of MMPs in the remodeling process after myocardial infarction. Finally, we speculate on the use of MMP inhibitors as potential therapy for heart failure.
引用
收藏
页码:201 / 210
页数:10
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