The role of matrix metalloproteinases in heart disease

Abstract

The heart can be subdivided into cellular and extracellular compartments. Approximately one third of cells from this cellular compartment are cardiomyocytes whereas two thirds of the cells are non-cardiomyocytes. Because of their dimensions, cardiomyocytes occupy two thirds of the total myocardial volume. Non-myocytes, predominantly fibroblasts, endothelial cells and to a 1esSer extent mast cells, macrophages and smooth muscle cells in the media of the myocardial vasculature, together with the extracellular matrix and tissue fluid, fill the remaining one third of cardiac tissue. The extracellular matrix compartment consists of a structural network of interstitial type I and III fibrillar collagens, which have a high rigidity and are extremely resistant to proteolytic digestion [ 11. Besides the fibrillar collagen network, the extracellular compartment consists of basement membranes, which in the heart surround individual cardiomyocytes and smooth muscle cells, and separate endothelial cells, even in capillaries, from the media or surrounding connective tissue. Basement membranes contain a structural backbone of type IV collagen to which other components like laminins, fibronectin, heparan sulphate proteoglycan, and other extracellular matrix components can attach 121. Type V collagen has been localized in basement membranes and interspersed in the interstitium [3]. Type VI collagen was found predominantly between cardiomyo-cytes linking basement membranes of the individual myocytes to the surrounding extracellular matrix and interstitial cells. The cardiac extracellu-