Dystrophin absence is implicated in the transition from physiological to pathological cardiac hypertrophy (547.4)

Hypertension causes cardiac hypertrophy, cardiac dysfunction, and heart failure (HF). The mechanisms implicated in the transition from physiological to pathological hypertrophy are still unknown. Growing evidence points out to the role of inappropriate mechanical coupling in the pathogenesis of HF and the cytoskeletal proteins as the most obvious candidates for intracelular remodeling. We investigated dystrophin and its potential role in the transition from physiological to pathological cardiac hypertrophy in rats submitted to chronic abdominal aorta stenosis. Wistar rats were submitted to abdominal aorta stenosis and killed at 30, 60 and 90 days post surgery (dps). The hearts were collected and Western blot and immunofluorescence were performed for dystrophin and calpain. Blood pressure was evaluated and cardiac function evaluate by echocardiography. Data were considered significant when p<0.05. At 90 dps 70% presented hypertrophied hearts (HH) and 30% hypertrophied+dilated hearts (DH), as evaluated by echocardiography. Blood pressure increased 53,42% (30d), 50,8% (60d) and 64,36% at 90dps. Dystrophin expression at 30, 60 dps and HH animals was the same as control, but decreased in DH animals. The ejection fraction was the same as control at 30 and 60dps, however it was reduced 35% at 90d in HH and 48% in DH. Loss of dystrophin could be partly responsible for the development of heart failure in rats submitted to chronic abdominal aorta stenosis. Thus, it is essential to define the mechanistic aspects of the pathophysiological processes involved in deterioration of cardiac function and design develop strategies to inhibit and/or reverse evolution of heart hypertrophy from compensated to decompensated phase. Grants from FAPESP 09/17787‐8; 10/19216‐5. Grant Funding Source : Supported by FAPESP 09/17787‐8; 10/19216‐5