Akt1-Mediated Skeletal Muscle Growth Enhances Blood Flow Recovery After Hind Limb Ischemia by Activating Heme Oxygenase-1 in Macrophage

Background: Supervised exercise is established intervention for patients with peripheral artery disease (PAD). In addition to aerobic exercise, it has been recognized that resistance exercise has beneficial effects for these patients. However, underling mechanism by which growing muscle improves blood flow is unclear. Hypothesis: Skeletal muscle growth enhances angiogenesis by modulating macrophage phenotype in ischemic lesion. Methods: We utilized skeletal muscle-specific, inducible Akt1 transgenic (Akt1 TG) mice, that can lead to the growth of functional skeletal muscle. Skeletal muscle specific heme oxygenase-1 (HO-1) knockout mice were generated by crossing HO-1-Flox mice with ACTA1-Cre mice. These mice were subjected to unilateral femoral artery ligation to induce hind limb ischemia, and blood flow recovery was assessed by laser Doppler and immunohistochemistry. Adenovirus-mediated Akt1 overexpression experiments were performed in C2C12 myotubes. Results: Blood flow recovery after hind limb ischemia ...