Structural and Functional Consequences of Myocardial Collagen Remodeling

Summary

Myocardial fibrillar collagens provide for muscle fiber and cardiac myocyte alignment and impart a tensile strength to the myocardium that maintains ventricular shape and size, and governs tissue stiffness. This network of collagen is intimately related with the myocyte and muscle fiber, as well as the coronary vasculature. Consisting primarily of collagen types I and III, fibrillar collagen is relatively inelastic and, even though normally present in relatively small amounts, plays an important role in the behavior of the ventricle during diastole. In renovascular and genetic hypertension, the hypertrophic response of the myocardium includes a progressive remodeling of the collagen matrix. Typically, there is an increase in collagen concentration, thickening of existing fibrillar collagen, and the addition of new collagen to all components of the matrix. The consequences of this remodeling are a stiffer myocardium and left ventricular diastolic dysfunction. These pathophysiologic aspects of the hypertrophic process are independent of the concomitant remodeling of the myocyte. Thus, an abnormal accumulation of interstitial collagen is a major distinguishing factor between physiologic and pathologic hypertrophy. Removal of less than half of the normal amount of collagen following collagenase activation results in a dilated ventricle with increased compliance. Collagenase activation, collagen degradation, and a dilated, thin-walled left ventricle are evident during ischemia, in dilated cardiomyopathy, and at end-stage heart failure. Thus, chronic changes in the shape and size of the heart are the result of an inadequate interstitial collagen matrix.