The molecular basis of myocardial hypertrophy.
Myocardial hypertrophy is an adaptive response of the heart to several pathological situations aimed at maintaining adequate cardiac contractile function. This process is characterized by complex qualitative and quantitative changes of both cardiomyocytes and nonmyocyte cardiac cells. The initial stimulus inducing these cellular responses is parietal stretch subsequent to either a pressure or volume overload. Many substances locally produced and acting in a paracrine-autocrine fashion are involved in the response to stretch by cardiac cells. The stretch, and, similarly, various growth factors (i.e. angiotensin II. endothelins, transforming growth factor beta, fibroblast growth factors), are able to modulate the expression of several protooncogenes in the cells of the myocardium, and these events are linked to the development of cardiac hypertrophy. Major goals of future research will include the detection of the molecular mechanisms enabling the cardiomyocyte, a terminally differentiated muscle cell, to respond to a mitogenic stimulus with hypertrophic rather than hyperplastic growth, as well as the identification of drugs able to block the evolution of hypertrophy to heart failure.