ABSTRACT
Hypertrophy is the common chronic adaptive response of the adult heart to injury or abnormal hemodynamic load and is physically manifested as increased cardiomyocyte size and protein content. Results from the Framingham Study show that myocardial hypertrophy predisposes to early death. Gq is the heterotrimeric G-protein that transduces signals from ligand-occupied heptahelical membrane receptors for angiotensin II, endothelin-1, alpha-adrenergic agonists, and other hormones known to provoke a hypertrophy response in cardiomyocytes. In vivo analysis of cardiac Gq/phospholipase-C/protein kinase C (PKC) signaling has been greatly advanced by utilization of transgenic techniques to overexpress Gq-coupled receptors, Gaq or its dominant negative inhibitor, or the downstream Gq effector, PKC, in the mouse heart. The transition from compensated hypertrophy to decompensated hypertrophy and dilated cardiomyopathy is classically associated with loss of cardiomyocytes and their replacement with fibrotic tissue. Studies over the past decade have increasingly supported an important pathophysiological role for cardiomyocyte apoptosis in heart failure decompensation.
