Cardiac hypertrophy can result from intrinsic and extrinsic stimuli. Extrinsic forms of hypertrophy are thought to be mediated by signals generated at the cell membrane. A variety of factors, including angiotensin II (Ang II), the adrenergic agonists phenylephrine (PE) and norepinephrine, endothelin-1 (ET-1), and the cytokine cardiotrophin act as potent hypertrophic agonists. In addition, perturbation of cardiac contractility due to altered sarcomeric function, as well as mechanical deformation, can result in cardiac hypertrophy. Mutations in MHC, 2 myosin light chains, tropomyosin, troponins T and I, myosin binding protein C, and α–cardiac actin have been identified in patients with cardiomyopathies. 7–9 Similarly, overexpression, misexpression, or deletion of several sarcomeric and cytoskeletal proteins in the hearts of transgenic mice result in forms of hypertrophy that mimic human heart disease. How perturbation in sarcomeric function is coupled to changes in cardiac gene expression is unclear, although it is well established that cardiomyocytes bearing mutant sarcomeric proteins exhibit alterations in Ca2+ handling and contractility, 10–13 which could be coupled to activation of the hypertrophic gene regulatory program.