AMPK regulates skeletal muscle capillarization and VEGF mRNA

Abstract

AMP-activated protein kinase (AMPK) is a metabolic fuel gauge important in maintaining intracellular energy homeostasis. Vascular endothelial growth factor (VEGF) is essential in the maintenance and expansion of skeletal muscle capillarization. Both VEGF and AMPK are increased in skeletal muscle in response to acute hypoxia and exercise. Pharmacological activation of AMPK increases skeletal muscle VEGF in vitro and augments angiogenesis in response to limb ischemia in vivo. We hypothesized that AMPK regulates basal skeletal muscle capillarization and the VEGF mRNA responses to acute hypoxia and exercise. The gastrocnemius from mice overexpressing an inactive AMPK α2 isoform (AMPK DN) or wild type (WT) littermates was analyzed for capillarization and the VEGF mRNA response to 2 hr of acute systemic hypoxia (6% O2) or 1 hr of acute treadmill exercise (55% of maximum). Muscle was harvested immediately-post hypoxia or exercise. Skeletal muscle capillarization and resting VEGF mRNA were lower in AMPK DN compared to WT. Acute hypoxia increased VEGF mRNA in WT, but this response was abolished in AMPK DN. Interestingly, the increase in VEGF mRNA with acute exercise tended (p=0.07) to be greater in AMPK DN compared to WT. These data suggest that AMPK regulates skeletal muscle capillarization and VEGF mRNA expression, though the direction of VEGF mRNA regulation appears dependent upon the conditions under investigation. Supported by NIA AG-21891, AHA Mid-Atlantic 0465415U and Gatorade Sports Science Institute Student Grant