The adult mammalian heart adapts to hemodynamic stress such as that induced by hypertension, valvular heart disease, and loss of contractile myocytes (as with myocardial infarction or cardiomyopathy), by developing compensatory hypertrophy of the remaining myocytes. 1 Alterations in gene expression appear to be a central feature of this adaptive physiological process, including alterations in contractile protein content and composition, the induction of embryonic markers such as atrial natriuretic factor, and the expression of proto-oncogenes and other immediate early genes (for a review, see Ref. 2). Although adaptive in origin, lowering wall stress by thickening the wall in concentric hypertrophy, or increasing chamber size to preserve forward stroke volume in volume overload or myocardial infarction, the development of ventricular hypertrophy also appears to be an early step in pathological ventricular remodeling, eventually leading to a decrease in global cardiac function.

The mechanisms by which the hemodynamic stress is sensed by myocytes and growth-related signals activated and integrated to selectively regulate the cardiac muscle gene program during myocardial hypertrophy are largely unknown. The relative absence of hypertrophy in the right heart following aortic constriction3 and the selective growth of the right ventricle after pulmonary artery banding4 suggests that circulating factors are unlikely to be principal mediators of these forms of hypertrophy. The underlying general hypothesis is that identifiable growth factors are produced by cardiac non-muscle cells or by the myocytes