Chronic Exercise Training Improved Aortic Endothelial and Mitochondrial Function via an AMPK alpha 2-Dependent Manner

Chronic exercise training is known to protect the vasculature; however, the underlying mechanisms remain obscure. The present study hypothesized that exercise may improve aortic endothelial and mitochondrial function through an adenosine monophosphate-activated protein kinase alpha 2 (AMPK alpha 2)-dependent manner. Ten-week-old AMPK alpha 2 knockout (AMPK alpha 2(-/-)) mice and age-matched wild-type (WT) mice were subjected to daily treadmill running for 6 weeks, and the thoracic aorta from these mice were used for further examination. Our results showed that exercise significantly promoted vasodilatation and increased expression and phosphorylation of endothelial nitric oxide synthase (eNOS), concomitant with increased AMPK alpha 2 expression in WT mice. These effects were not observed in AMPK alpha 2(-/-) mice. Furthermore, exercise training increased thoracic aortic mitochondria' content as indicated by increased Complex I and mitochondria' DNA (mtDNA) in WT mice but not in AMPK alpha 2(-/-) mice. This may be caused by decreased mitochondria' autophagy since the expression of BH3 domain-containing BCL2 family members BNIP3-like (BNIP3L) and LC3B were decreased in WT mice with exercise. And these changes were absent with AMPK alpha 2 deletion in mice. Importantly, exercise increased the expression of manganous superoxide dismutase (MnSOD) and catalase, suggesting that mitochondria' antioxidative capacity was increased. Notably, the improved antioxidative capacity was lost in AMPK alpha 2(-/-) mice with exercise. In conclusion, this study illustrated that AMPK alpha 2 plays a critical role in exercise-related vascular protection via increasing endothelial and mitochondria' function in the artery.National Natural Science Foundation of China [81100184, 81230071, 81300089, 81200203, 91539202, 81570221]; Scientific Fund of Shanghai Jiao Tong University School of Medicine [14XJ10042]; Pujiang Program of the Shanghai Science and Technology Committee [14PJ1406400]; Scientific Research Foundation for the Returned Overseas Chinese Scholars of the State Education Ministry; Shanghai Medical Bureau Fund [201540037]SCI(E)ARTICLEzhangyy@bjmu.edu.cn; gaopingjin@sibs.ac.cn