Abstract 13445: Akt1-Mediated Skeletal Muscle Growth Prevents Left Ventricular Remodeling after Experimental Myocardial Infarction
Introduction: It is well known that aerobic endurance exercise can attenuate unfavorable myocardial remodeling post myocardial infarction (MI). In contrast, little is known about the effect of resistance exercise training on these processes, because animal model that can assess the molecular relationship between muscle growth and cardiac remodeling are lacking.
Hypothesis: Skeletal muscle growth can prevent cardiac remodeling after mouse model of myocardial infarction.
Methods: We used skeletal muscle-specific, conditional Akt1 transgenic (TG) mice that can induce the growth of functional skeletal muscle by switching Akt1 signaling on or off. Male non-induced TG mice and their littermates (control) were subjected to left anterior descending coronary artery ligation. Two days after operation, mice were provided doxycycline in their drinking water to induce Akt1 transgene in skeletal muscle-specific manner. Cardiac function and remodeling were assessed by echocardiography, histological and gene expression analysis 2 weeks after MI.
Results: Activation of Akt1 signaling for 2 weeks led to an increase in muscle mass (6.9±0.5 vs. 5.5±0.1 mg/g, gastrocnemius muscle weight/body weight, p<0.01. n=7). There were no significant differences in body weight (BW), heart rate or echocardiographic parameters between TG and control mice at 2 weeks after MI. But, the increase in heart weight/BW ratio was significantly smaller in TG mice than that in control mice (5.6±0.2 vs 4.9±0.2 mg/g, p<0.05. n=7). Lung wet weight/BW ratio was significantly decreased in TG mice compared with that in control mice, indicating an improvement in pulmonary congestion. MI-induced upregulation of BNP and collagen III transcript expression was significantly attenuated in TG mice (P<0.05. n=7). Comprehensive protein array analysis demonstrated that panels of angiogenic factors were increased in TG mice in serum and skeletal muscle. Furthermore, endothelial progenitor cell (EPC) mobilization to peripheral circulation was 2.1-folds greater in TG mice than in control mice (P<0.05. n=5).
Conclusion: Akt1-mediated skeletal muscle growth attenuates cardiac remodeling after MI probably through secretion of a panel of angiogenetic factors and induction of EPC mobilization.
- © 2010 by American Heart Association, Inc.