RALT Specifically Halts Maladaptive Cardiac Hypertrophy

Abstract

The adult heart enlarges and increases in weight in response to ischemic stress and hypertension, a process termed cardiac hypertrophy. However, the heart also increases in size after regular physiological exercise. Cardiac hypertrophy is recognized as an important process in the development of heart failure. Initial results pointed to a clear signaling pattern of physiological hypertrophy after training versus pathological hypertrophy after damage. Although the signaling mechanisms involved have been studied for more than a decade, there is no clear distinction at the molecular level of physiological and pathological hypertrophy.1 Rather, the balance between signaling pathways preventing deterioration and pathways activated in association with preserving left ventricular function is regarded as critical. Accordingly, the terms adaptive and maladaptive were introduced to reflect these processes, respectively.2 A potential treatment avenue could be to selectively identify pathways involved in maladaptive hypertrophy that could be blocked. Alternatively, enhancing signaling pathways specifically involved in adaptive hypertrophy might allow us to conserve left ventricular function. Cai et al have identified a new target in cardiac hypertrophy: the receptor-associated late transducer (RALT).3 RALT appears to be a specific antagonist of maladaptive hypertrophy (Figure). Mechanistically, RALT functions as a negative regulator of epidermal growth factor receptor-mediated signaling not only in the heart but in other organs as well. The investigators used angiotensin II and isoproterenol as stimuli for stress-induced, maladaptive left ventricular remodeling in transgenic mice overexpressing RALT under the control of the α-myosin heavy …