ROLE OF EXTRACELLULAR-MATRIX PROTEINS IN HEART FUNCTION

The cardiac interstitium is populated by nonmyocyte cell types includi ng transcriptionally active cardiac fibroblasts and endothelial cells. Since these cells are the source of many components of the cardiac ex tracellular matrix, and because changes in cardiac extracellular matri x are suspected of contributing to the genesis of cardiovascular compl ications in disease states such as diabetes, hypertension, cardiac hyp ertrophy and congestive heart failure, interest in the mechanisms of a ctivation of fibroblasts and endothelial cells has led to progress in understanding these processes. Recent work provides evidence for the r ole of the renin-angiotensin-aldosterone system in the pathogenesis of abnormal deposition of extracellular matrix in the cardiac interstiti um during the development of inappropriate cardiac hypertrophy and fai lure. The cardiac extracellular matrix is also known to change in resp onse to altered cardiac performance associated with post-natal aging, and in response to environmental stimuli including intermittent hypoxi a and abnormal nutrition. It is becoming clear that the extracellular matrix mainly consists of molecules of collagen types I and III; they form fibrils and provide most of the connective material for tying tog ether myocytes and other structures in the myocardium and thus is invo lved in the transmission of developed mechanical force. The data avail able in the literature support the view that the extracellular matrix is a dynamic entity and alterations in this structure result in the de velopment of heart dysfunction.