Emerging role of matrix metalloproteinases in the pathophysiology of cardiac diseases

As other organs, the heart is composed of highly differentiated, very specialized parenchymal cells (cardiomyocytes) surrounded by stroma consisting of extracellular matrix (ECM), tissue fluid and undifferentiated, pluripotent mesenchymal cells.

The maintenance of matrix integrity involves the synthesis and degradation of its major components, including collagens, glycoproteins, glycosaminoglycans and proteoglycans. The ECM-degrading proteinases can be subdivided into three main classes: serine proteinases, metalloproteinases and cysteine proteinases. Matrix metalloproteinases (MMPs) make up a family of more than 20 zinc-containing endoproteinases that can be subdivided into four groups based on their substrate specificity and primary structure.

The first group, the collagenases, include MMP-1 (interstitial collagenase), MMP-8 (neutrophil collagenase) and MMP-13 (collagenase 3), which can all cleave fibrillar collagens (types I, II and III). Group 2, the gelatinases (MMP-2 and MMP-9), is well known for its ability to degrade gelatins and type IV collagen in basement membranes. Group 3 constitutes the stromelysins (MMP-3, MMP-10 and MMP-11), so named because they are active against a broad spectrum of ECM components, including proteoglycans, laminins, fibronectin, vitronectin and some types of collagens. Group 4 contains the membrane-type MMPs (MT-MMPs), which degrade several ECM components and are also able to activate other MMPs.

CITATION  Eur J Clin Invest. 2002 May;32(5):291-4