Novel Aspects of Mechanical Signaling in Cardiac Tissue

Cardiac hypertrophy is a common outcome of hypertension or myocardial infarction and a major contributor to cardiovascular morbidity and mortality. Under increased hemodynamic load, the heart compensates by undergoing compensatory hypertrophy, a response that restores lost function and normalizes wall stress. Although initially beneficial, hypertrophy is an independent risk factor for heart failure since sustained cardiac hypertrophy can lead to decompensation and subsequent failure. Since cardiac myocytes are terminally differentiated and lose the ability to replicate soon after birth, these cells respond to increased work load by an increase in cell size. An intriguing and unresolved aspect of this process has been the ability of myocytes to sense mechanical stimuli and convert it into intracellular growth signals. Recent studies have focused on identifying the underlying mechanisms responsible for cardiac hypertrophy. A number of mechanosensors and signal transduction pathways have been identified as potential regulators of the hypertrophic response. Integrins and stretch-activated calcium channels have been shown to couple to low-molecular weight GTPases (Ras, Rae, RhoA), mitogen-activated protein kinases and protein kinase C. This review will discuss the key aspects of these signal transduction mechanisms.