Matrix metalloproteinases and myocardial infarction

Abstract

A cute myocardial infarction (AMI) is one of the most important health problems in many nations around the world. It may be found in many age groups, but is predominant among elderly people (1). The incidence of AMI has been increasing, possibly due to the changes in lifestyle and dietary intake that lead to an increase in coronary risk factors for cardiovascular disease.AMI has devastating consequences in the early phase, such as cardiac rupture, and in the chronic phase, such as chronic heart failure, for which the risk is mainly determined by infarct size (2). Larger infarct size induces gross morphological, histological and molecular changes of the infarcted and noninfarcted regions. These changes are known as the cardiac remodelling process. The degree of cardiac remodelling is closely related to the incidence of cardiac arrhythmias, heart failure and mortality (3). Cardiac remodelling involves changes in cardiac myocytes and in the extracellular matrix (ECM). The ECM contains a wide array of structural proteins, such as fibrillar collagen, proteoglycans and glycosaminoglycans, and serves as a reservoir for biologically active molecules. Because myocardial collagens maintain the structural integrity of adjoining myocytes and provide the means by which myocyte shortening is translated into cardiac pump function, changes in the ECM result in a loss of normal structural and functional myocardium.Matrix metalloproteinase (MMP) is a proteolytic enzyme that has been identified in the myocardium, and is likely to contribute to ECM changes and myocardial remodelling. In the past few decades, growing evidence from basic and clinical studies have demonstrated the important role of MMPs in the progression of left ventricular dimension, remodelling and mortality following AMI. In the present article, MMP expression after AMI and its role as a possible prognostic marker are reviewed. Currently available data regarding the role of MMP inhibitors as a possible novel therapeutic intervention are also discussed. Acute myocardial infarction (AMI) is currently one of the most important health problems in many countries around the world. Following AMI, many cytokines and proteolytic enzymes are released. Among these, matrix metalloproteinases (MMPs) are important proteolytic enzymes that lead to degradation of the extracellular matrix and to changes in cardiomyocytes in both infarcted and noninfarcted myocardium. This process is known as cardiac remodelling. It has been demonstrated that more than one type of MMP is present in the circulation after cardiomyocyte injury. A number of studies have demonstrated the correlations between these MMP levels and the severity of a coronary lesion, the progression of left ventricular dimension and the survival rate following AMI in both animal and human studies. MMPs have also been proposed as a possible novel prognostic indicator for myocardial infarction patients. Although the use of MMP inhibitors to improve cardiac outcome in AMI patients has been investigated, discrepancies in the re...

Soluble biglycan as a biomarker of inflammatory renal diseases

“…Disruption of this interaction triggers the cleavage of the N-terminus, leading to enzyme activation (Van Wart and Birkedal-Hansen, 1990). There are more than 25 members currently in the MMP family (Phatharajaree et al, 2007). …”

Molecular Imaging of the Cardiac Extracellular Matrix

“…Although MMP activity can counterbalance the increased ECM deposition, excessive ECM degradation may result in wall thinning, dilatation, and predispose to heart failure, or aneurysm formation and cardiac rupture. 18,19 MMPs are inhibited by tissue inhibitors of metalloproteinases 1-4 18 . MMP imaging has taken advantage of 2 principles: (1) creating tissue inhibitors of metalloproteinase-like peptides that inhibit either a wide range of MMPs or inhibit a specific MMP; these peptides if appropriately labeled may allow assessment of the magnitude of MMP production, or (2) using a substrate amenable to proteolytic cleavage by MMP, the cleaved reporter molecule accumulates in the tissue and can be detected by imaging.…”

“…Matrix metalloproteinases (MMPs) are also upregulated in cardiac diseases, 18 which result in ECM degradation that facilitates adaptive changes (such as removal of cellular debris by inflammatory cells and migration of myofibroblasts) and also contributes to weakening the structure, promoting dilatation and even aneurysm formation. 18,19 Because of its excellent spatial and temporal resolution, MRI has evolved as the gold standard for structural cardiac imaging. Using late-gadolinium enhancement (LGE), MRI can accurately detect fibrosis and quantify ECM volume.…”

Matrix Metalloproteinases: Drug Targets for Myocardial Infarction

“…TIMP-2 potentially inhibits all MMPs but has a higher affinity to MMP-2 than MMP-9. TIMP-3 has been shown to bind to MMP-1, -2, -3, -9, and -13 and TIMP-4 inhibits MMP-1, -3, -7, and -9 [8].…”