Akt1-mediated skeletal muscle growth attenuates cardiac dysfunction and remodeling after experimental myocardial infarction.

BACKGROUND: It is appreciated that aerobic endurance exercise can attenuate unfavorable myocardial remodeling following myocardial infarction. In contrast, little is known about the effects of increasing skeletal muscle mass, typically achieved through resistance training, on this process. Here, we utilized transgenic (TG) mice that can induce the growth of functional skeletal muscle by switching Akt1 signaling in muscle fibers to assess the impact of glycolytic muscle growth on post-myocardial infarction cardiac remodeling. METHODS AND
RESULTS: Male-noninduced TG mice and their nontransgenic littermates (control) were subjected to left anterior coronary artery ligation. Two days after surgery, mice were provided doxycycline in their drinking water to activate Akt1 transgene expression in a skeletal muscle-specific manner. Myogenic Akt1 activation led to diminished left ventricular dilation and reduced contractile dysfunction compared with control mice. Improved cardiac function in Akt1 TG mice was coupled to diminished myocyte hypertrophy, decreased interstitial fibrosis, and increased capillary density. ELISA and protein array analyses demonstrated that serum levels of proangiogenic growth factors were upregulated in Akt1 TG mice compared with control mice. Cardiac eNOS was activated in Akt1 TG mice after myocardial infarction. The protective effect of skeletal muscle Akt activation on cardiac remodeling and systolic function was abolished by treatment with the eNOS inhibitor l-NAME.
CONCLUSIONS: Akt1-mediated skeletal muscle growth attenuates cardiac remodeling after myocardial infarction and is associated with an increased capillary density in the heart. This improvement appears to be mediated by skeletal muscle to cardiac communication, leading to activation of eNOS-signaling in the heart.