Role of extracellular matrix proteins in heart function

Abstract

The cardiac interstitium is populated by nonmyocyte cell types including transcriptionally active cardiac fibroblasts and endothelial cells. Since these cells are the source of many components of the cardiac extracellular matrix, and because changes in cardiac extracellular matrix are suspected of contributing to the genesis of cardiovascular complications in disease states such as diabetes, hypertension, cardiac hypertrophy and congestive heart failure, interest in the mechanisms of activation of fibroblasts and endothelial cells has led to progress in understanding these processes. Recent work provides evidence for the role of the renin-angiotensin-aldosterone system in the pathogenesis of abnormal deposition of extracellular matrix in the cardiac interstitium during the development of inappropriate cardiac hypertrophy and failure. The cardiac extracellular matrix is also known to change in response to altered cardiac performance associated with post-natal aging, and in response to environmental stimuli including intermittent hypoxia 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 typing together myocytes and other structures in the myocardium and thus is involved in the transmission of developed mechanical force. The data available in the literature support the view that the extracellular matrix is a dynamic entity and alterations in this structure result in the development of heart dysfunction.

Effect of Captopril in L-Name-Induced Hypertension on the Rat Myocardium, Aorta, Brain and Kidney

“…Protein synthesis may be affected in all cell types, while cell division has been found to occur in certain cells of different tissues: fibrocytes in the LV (Pelouch et al 1994), smooth muscle cells and fibrotic cells in the aorta, mesangial cells in the kidney (Hropot et al 1994), and conceivably fibrocytes in the brain. In our previous work (Bab al et al 1997), proliferation cell nuclear antigen immunohistochemistry indicated positive cells in the fibrotic tissue of the myocardium as well as in the media of coronary arteries and aorta.…”

Matrix Metalloproteinases: Drug Targets for Myocardial Infarction

“…The myocardial ECM directs contractile force generated by cardiomyocytes and sustains shear stress generated by cardiomyocytes. In addition, the myocardial ECM produces and maintains certain levels of a variety of growth factors, as well as modulates cell proliferation and differentiation, ECM synthesis and remodeling [3][4][5].…”

Endothelial relaxation is disturbed by oxidative stress in the diabetic rat heart: influence of tocopherol as antioxidant

“…Inhibition of NO synthesis has been E R6sen et al: Endothelial relaxation is disturbed in diabetes shown to lead to an activation of the sympathetic nervous system [26], which is a frequent complication in human and experimental diabetes [27]. It has been suggested, furthermore, that in diabetes an activation of the sympathetic nervous system contributes to myocardial damage either by the generation of cytotoxic free radicals derived from catecholamines [28] or by induction of hypertrophy and growth factors resulting in an increased expression of collagen in myocardium [27,29,30]. Prevention of NO inactivation by oxidative stress is therefore expected to protect the heart in diabetes by at least two different mechanisms: directly, by restoring the vasodilatory effect of NO and indirectly, by prevention of a cascade of events associated with the excessive activation of the sympathetic nervous system.…”