Myocardium is comprised of a number of cell types. Although most plentiful by volume, cardiac myocytes are greatly outnumbered by nonmyocyte cells, the latter constituting approximately 70% of all myocardial cells, of which approximately 90% are cardiac fibroblasts (CFBs). To maintain the integrity of the cardiac extracellular matrix (ECM) is one of the primary functions of cardiac fibroblasts. ECM represents a network structure that provides the structural and functional integrity to the heart. Besides that, it also contains a high number of cytokines and growth factors with effects on cardiac function and cardiac cells. Cardiac ECM also mediates the mechanical connection between the cardiomyocytes, CFBs, and blood. In addition to producing ECM proteins, CFBs also produce ECM-regulatory proteins -matrix metalloproteinases (MMPs), which can degrade ECM proteins -and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs). To date, 26 MMPs have been cloned and characterized in vertebrates. From these, MMP1, MMP3, MMP8, MMP13, MMP2, MMP9, MMP12, MMP28, and the membrane-type MMPs (MT1-MMP/MMP14) have been identified to be involved in the myocardial remodeling. The role of higher MMPs in the cardiovascular system is less well explored.
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