MYOCARDIAL COLLAGEN REMODELING AND LEFT-VENTRICULAR DIASTOLIC FUNCTION

1. The myocardial collagen matrix is an active participant in determining ventricular architecture and diastolic function, and myocardial structural integrity and mechanical properties. It consists of a network of fibrillar collagen which is intimately related with the myocyte, myofibril and muscle fiber as well as the coronary vasculature. Consisting primarily of collagen types I and III, this material exhibits a high tensile strength which, even though normally present in relatively small amounts, plays an important role in the behavior of the ventricle during diastole. 2. Removal of less than half of the normal amount of collagen results in a dilated ventricle with increased compliance. Collagen degradation of this magnitude and similar myocardial and ventricular histologic and functional alterations are evident during ischemia and in dilated cardiomyopathy. Thus, it would appear that a chronic change in the shape and size of the heart must be preceded by alterations in the interstitial collagen matrix. 3. With elevations in the circulating levels of angiotensin and/or mineralocorticoids, the hypertrophic response of the myocardium to the accompanying hypertension includes a progressive remodeling of the collagen component. Typically there is an increase in collagen concentration, thickening of existing fibrillar collagen and the addition of new collagen at all levels of the matrix. The consequences of this remodeling are an adverse alteration of the passive mechanical properties of the myocardium and LV diastolic dysfunction. This pathophysiologic aspect of the hypertrophic process is independent of the concomitant remodeling of the myocyte. Thus, an alteration in the extracellular matrix which results in an abnormal accumulation of interstitial collagen is a major distinguishing factor between physiologic and pathologic hypertrophy.