Chen Xiaohui, An Xiangbo, Chen Dongrui, Ye Maoqing, Shen Weili, Han Weiqing, Zhang Youyi, Gao Pingjin
Laboratory of Vascular Biology and Key Laboratory of Stem Cell Biology, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, University of Chinese Academy of Sciences Shanghai, China.
Institute of Vascular Medicine, Peking University Third Hospital Beijing, China.
Front Physiol. 2016 Dec 21;7:631. doi: 10.3389/fphys.2016.00631. eCollection 2016.
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 α2 (AMPKα2)-dependent manner. Ten-week-old AMPKα2 knockout (AMPKα2) 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 AMPKα2 expression in WT mice. These effects were not observed in AMPKα2 mice. Furthermore, exercise training increased thoracic aortic mitochondrial content as indicated by increased Complex I and mitochondrial DNA (mtDNA) in WT mice but not in AMPKα2 mice. This may be caused by decreased mitochondrial 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 AMPKα2 deletion in mice. Importantly, exercise increased the expression of manganous superoxide dismutase (MnSOD) and catalase, suggesting that mitochondrial antioxidative capacity was increased. Notably, the improved antioxidative capacity was lost in AMPKα2 mice with exercise. In conclusion, this study illustrated that AMPKα2 plays a critical role in exercise-related vascular protection via increasing endothelial and mitochondrial function in the artery.
已知慢性运动训练可保护血管系统；然而，其潜在机制仍不清楚。本研究假设运动可能通过一种依赖于单磷酸腺苷激活蛋白激酶α2（AMPKα2）的方式改善主动脉内皮和线粒体功能。将10周龄的AMPKα2基因敲除（AMPKα2 -/-）小鼠和年龄匹配的野生型（WT）小鼠每天进行跑步机跑步训练6周，然后取这些小鼠的胸主动脉用于进一步检测。我们的结果表明，运动显著促进血管舒张，并增加内皮型一氧化氮合酶（eNOS）的表达和磷酸化，同时WT小鼠中AMPKα2的表达增加。在AMPKα2 -/-小鼠中未观察到这些效应。此外，运动训练增加了胸主动脉的线粒体含量，表现为WT小鼠中复合物I和线粒体DNA（mtDNA）增加，而AMPKα2 -/-小鼠中未增加。这可能是由于线粒体自噬减少所致，因为运动的WT小鼠中含BH3结构域的BCL2家族成员BNIP3样蛋白（BNIP3L）和LC3B的表达降低。而在基因敲除AMPKα2的小鼠中未出现这些变化。重要的是，运动增加了锰超氧化物歧化酶（MnSOD）和过氧化氢酶的表达，表明线粒体抗氧化能力增强。值得注意的是，运动的AMPKα2 -/-小鼠中这种改善的抗氧化能力丧失。总之，本研究表明AMPKα2在运动相关的血管保护中起着关键作用，其通过增强动脉中的内皮和线粒体功能来实现。
