Mitochondrial Oxidative Stress, Mitochondrial DNA Damage and Their Role in Age-Related Vascular Dysfunction.
Mitochondrial Oxidative Stress, Mitochondrial DNA Damage and Their Role in Age-Related Vascular Dysfunction.
复制标题
线粒体氧化应激，线粒体DNA损伤及其在与年龄相关的血管功能障碍中的作用。
DOI：
10.3390/ijms160715918
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发表时间：
2015-07-13
影响因子：
5.6
通讯作者：
Steven S
中科院分区：
文献类型：
--
作者：
Mikhed Y;Daiber A;Steven S
老年人口中心血管疾病的发病率显著增加。高血压、动脉粥样硬化或糖尿病等未来心血管事件的危险因素和预测因素在老年人中出现的频率更高。血管老化的主要决定因素是内皮功能障碍，其特征是内皮依赖信号过程受损。活性氧（ROS）的产生增加导致氧化应激、一氧化氮（NO）信号的丧失、内皮屏障功能的丧失和白细胞向血管壁的浸润，这解释了老年血管系统的低度炎症特征。我们在这里讨论不同来源的活性氧对血管老化的重要性，以及它们对老年人群心血管风险增加的贡献，特别强调线粒体活性氧的形成和线粒体DNA的氧化损伤。此外，线粒体与烟酰胺腺苷二核苷酸磷酸（NADPH）氧化酶的相互作用（串扰）也被强调。目前血管老化的概念，心血管事件发展的后果和ROS的特殊作用是在细胞培养实验，动物研究和临床试验的基础上进行评估。目前的数据表明，氧化应激对最大健康寿命（健康衰老）的作用比对最大寿命的作用更重要。
The prevalence of cardiovascular diseases is significantly increased in the older population. Risk factors and predictors of future cardiovascular events such as hypertension, atherosclerosis, or diabetes are observed with higher frequency in elderly individuals. A major determinant of vascular aging is endothelial dysfunction, characterized by impaired endothelium-dependent signaling processes. Increased production of reactive oxygen species (ROS) leads to oxidative stress, loss of nitric oxide (•NO) signaling, loss of endothelial barrier function and infiltration of leukocytes to the vascular wall, explaining the low-grade inflammation characteristic for the aged vasculature. We here discuss the importance of different sources of ROS for vascular aging and their contribution to the increased cardiovascular risk in the elderly population with special emphasis on mitochondrial ROS formation and oxidative damage of mitochondrial DNA. Also the interaction (crosstalk) of mitochondria with nicotinamide adenosine dinucleotide phosphate (NADPH) oxidases is highlighted. Current concepts of vascular aging, consequences for the development of cardiovascular events and the particular role of ROS are evaluated on the basis of cell culture experiments, animal studies and clinical trials. Present data point to a more important role of oxidative stress for the maximal healthspan (healthy aging) than for the maximal lifespan.