Akt1-mediated skeletal muscle growth attenuates cardiac dysfunction and remodeling after experimental myocardial infarction.
نویسندگان
چکیده
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.
منابع مشابه
Akt1-Mediated Skeletal Muscle Growth Attenuates Cardiac Dysfunction and Remodeling after Experimental Myocardial Infarction Araki et al: Muscle Growth Attenuates Cardiac Remodeling
Background It is appreciated that aerobic endurance exercise can attenuate unfavorable myocardial remodeling post myocardial infarction (MI). 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 switchi...
متن کاملChronic Akt1 Deficiency Attenuates Adverse Remodeling and Enhances Angiogenesis After Myocardial Infarction Vandoorne et al: Cardiac Protective Effects of Akt1 Deficiency
متن کامل
Effects of Doxycycline on Cx43 Distribution and Cardiac Arrhythmia Susceptibility of Rats after Myocardial Infarction
Effects of Doxycycline on Cx43 Distribution and Cardiac Arrhythmia Susceptibility of Rats after Myocardial Infarction Abstract: This study aimed to observe the effects of doxycycline (DOX) on gap junction remodeling after MI and the susceptibility of rats to cardiac arrhythmia. The proximal left anterior descending coronary artery of rats was ligated to establish a myocardial infarction animal...
متن کاملEffects of Doxycycline on Cx43 Distribution and Cardiac Arrhythmia Susceptibility of Rats after Myocardial Infarction
Effects of Doxycycline on Cx43 Distribution and Cardiac Arrhythmia Susceptibility of Rats after Myocardial Infarction Abstract: This study aimed to observe the effects of doxycycline (DOX) on gap junction remodeling after MI and the susceptibility of rats to cardiac arrhythmia. The proximal left anterior descending coronary artery of rats was ligated to establish a myocardial infarction animal...
متن کاملTargeted inhibition of activin receptor-like kinase 5 signaling attenuates cardiac dysfunction following myocardial infarction.
Following myocardial infarction (MI), the heart undergoes a pathological process known as remodeling, which in many instances results in cardiac dysfunction and ultimately heart failure and death. Transforming growth factor-beta (TGF-beta) is a key mediator in the pathogenesis of cardiac remodeling following MI. We thus aimed to inhibit TGF-beta signaling using a novel orally active TGF-beta ty...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Circulation. Heart failure
دوره 5 1 شماره
صفحات -
تاریخ انتشار 2012