Physical exercise attenuates age-associated reduction in endothelium-reparative capacity of endothelial progenitor cells by increasing CXCR4/JAK-2 signaling in healthy men
Physical exercise attenuates age-associated reduction in endothelium-reparative capacity of endothelial progenitor cells by increasing CXCR4/JAK-2 signaling in healthy men
复制标题
体育锻炼通过增加健康男性的 CXCR4/JAK-2 信号传导，减轻与年龄相关的内皮祖细胞内皮修复能力的下降
DOI：
10.1111/j.1474-9726.2011.00758.x
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发表时间：
2012-02-01
期刊：
影响因子：
7.8
通讯作者：
Tao, Jun
中科院分区：
文献类型：
--
作者：
Xia, Wen-Hao;Li, Jing;Tao, Jun
内皮祖细胞（Endothelial progenitor cells, EPCs）在内皮损伤的修复中起着重要作用。衰老与EPC功能障碍有关。体育锻炼对EPC活动有有益影响。然而，体育锻炼是否能增强衰老健康男性EPCs的内皮修复能力尚不清楚。在这里，我们研究了体育锻炼对人内皮细胞再内皮化能力和CXC趋化因子受体4 （CXCR4）信号传导的影响。在12周运动前后，分别从老年人和年轻人身上分离EPCs。测定EPCs在颈动脉损伤小鼠模型中的体外功能和体内再内皮化能力。检测CXCR4及其下游信号靶点Janus kinase-2 （JAK-2）的表达。运动前，老年男性EPCs体外功能和体内再内皮化能力明显低于年轻男性。运动干预后，老年男性EPCs体外功能和体内再内皮化能力明显增强。体育锻炼增加了较高的CXCR4蛋白表达和较高的EPCs JAK-2磷酸化水平。EPCs再内皮化能力的增强与CXCR4/JAK-2信号的上调和内皮功能的改善密切相关。这项研究首次证明，体育锻炼通过增加CXCR4/JAK-2信号，可以减弱内皮细胞修复能力的年龄相关性下降。我们的研究结果为体育锻炼作为一种生活方式干预策略促进老年人血管健康的新机制提供了见解。
Endothelial progenitor cells (EPCs) play an important role in repairing endothelial injury. Aging is associated with EPC dysfunction. Physical exercise has a beneficial impact on EPC activity. However, whether physical exercise can enhance the endothelial repair capacity of EPCs in healthy men with aging is not clear. Here, we investigated the effects of physical exercise on reendothelialization capacity and CXC chemokine receptor four (CXCR4) signaling in human EPCs. Before and after 12-week exercise, EPCs were isolated from elderly and young men. In vitro function and in vivo reendothelialization capacity of EPCs in a mouse model of carotid artery injury were measured. The expression of CXCR4 and its downstream signaling target Janus kinase-2 (JAK-2) were determined. Before exercise, in vitro function and in vivo reendothelialization capacity of EPCs were significantly reduced in elderly men compared with young men. After exercise intervention, in vitro function and in vivo reendothelialization capacity of EPCs from elderly men were markedly enhanced. Physical exercise increased a higher CXCR4 protein expression and higher JAK-2 phosphorylation levels of EPCs. The augmentation in reendothelialization capacity of EPCs was closely correlated with the upregulation of CXCR4/JAK-2 signaling and improvement of endothelial function. This study demonstrates for the first time that physical exercise attenuates age-associated reduction in endothelium-reparative capacity of EPCs by increasing CXCR4/JAK-2 signaling. Our findings provide insight into the novel mechanisms of physical exercise as a lifestyle intervention strategy to promote vascular health in aging population.