Abstract 13479: AMP-activated Protein Kinase Mediates Vascular Protective Effects During Exercise Training
Background: Regular physical activity is known to protect the vasculature by antioxidative effects and upregulation of endothelial nitric oxide synthase. During skeletal muscle contraction, the AMP activated protein kinase is being activated and improves glucose uptake and metabolism. This may explain the positive effects of exercise regarding metabolic control in diabetics. Since the AMP activated proteinkinase (AMPK) is also an important mediator of angiogenesis and eNOS activation, we examined the vascular effects of AMPK deletion during chronic exercise training.
Methods and Results: Since vascular cells almost exclusively harbour the alpha1AMPK isoform, alpha1AMPK knockout and corresponding wildtype mice were used to study the effects of decreased vascular AMPK activity. Mice underwent voluntary exercise training in running wheels (mean running distance was 4.2 + 0.8 km/d in wildtype mice and 4.0 + 0.9 km/d in alpha1AMPK knockout mice (p=ns)). Exercise training significantly improved endothelial function and increased plasma nitrite production in wildtype mice, while it had no effect on these parameters in alpha1AMPK knockout mice. In addition, regular physical activity caused an upregulation of AMPK protein and phosphorylation at threonin172, which was associated with increased aortic eNOS expression, serine1177 eNOS phosphorylation and increased number of endothelial progenitor cells in peripheral blood (Sca-1/VEGF-R2 positive cells). All these effects were absent after alpha1AMPK deletion, which resulted in an appr. 90% reduction of total aortic AMPK expression. In addition, regular physical activity resulted in a significant decrease of aortic ROS production in wildtype mice assessed by dihydroethidium staining or lucigenin chemiluminescence, but had no effect in alpha1AMPK knockout mice.
Conclusions: Intact AMPK signalling is required for the manifestation of vascular protective effects during exercise training. Pharmacological AMPK activation might be a novel approach in the near future to simulate the beneficial effects of physical activity.
- © 2010 by American Heart Association, Inc.