title: Akt1-mediated skeletal muscle growth attenuates cardiac dysfunction and remodeling after experimental myocardial infarction.
abstract: 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.
  
  
  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.
authors.affiliation: Department of Cardiovascular Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Araki
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Izumiya
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Hanatani
authors.forename: Taku
authors.initials: T
authors.lastname: Rokutanda
authors.forename: Hiroki
authors.initials: H
authors.lastname: Usuku
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Akasaki
authors.forename: Toru
authors.initials: T
authors.lastname: Takeo
authors.forename: Naomi
authors.initials: N
authors.lastname: Nakagata
authors.forename: Kenneth
authors.initials: K
authors.lastname: Walsh
authors.forename: Hisao
authors.initials: H
authors.lastname: Ogawa
mesh_terms: D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016220:Fibroblast Growth Factor 1 / Q000097:blood; D006352:Heart Ventricles / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D023421:Models, Animal; D018482:Muscle, Skeletal / Q000187:drug effects / Q000254:growth & development*; D009203:Myocardial Infarction / Q000150:complications* / Q000503:physiopathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology / Q000517:prevention & control*; D020257:Ventricular Remodeling / Q000502:physiology
chemical_list: D004791:Enzyme Inhibitors; D042461:Vascular Endothelial Growth Factor A; D016220:Fibroblast Growth Factor 1; D052250:Nitric Oxide Synthase Type III; C514862:Akt1 protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D019331:NG-Nitroarginine Methyl Ester