Aging and vascular endothelial function in humans.
Aging and vascular endothelial function in humans.
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DOI：
10.1042/cs20100476
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发表时间：
2011-05
期刊：
影响因子：
--
通讯作者：
Donato AJ
中科院分区：
文献类型：
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作者：
Seals DR;Jablonski KL;Donato AJ
高龄是心血管疾病发展的主要危险因素。这在一定程度上可归因于血管内皮功能障碍的发展，正如外周动脉EDD（内皮依赖性扩张）因化学[通常是乙酰胆碱]或机械（血管内剪切）刺激而减少所表明的那样。氧化应激导致的内皮合成的扩张分子NO（一氧化氮）的生物利用度降低是EDD随年龄降低的关键机制。血管氧化应激随着年龄的增长而增加，因为活性氧（如超氧化物）的产生增加，而抗氧化防御没有代偿性的增加。超氧化物产生增加的来源包括氧化酶NADPH氧化酶的上调，正常产生NO的酶eNOS（内皮NO合成酶）的解偶联（由于辅助因子四氢生物蝶呤的可用性降低）和氧化磷酸化过程中线粒体合成的增加。强效内皮来源的收缩因子ET-1（内皮素-1）的生物活性增加，内皮细胞对扩张性前列腺素的产生/反应性降低，血管炎症的发展，AGEs（晚期糖基化终产物）的形成，内皮细胞凋亡率增加和雌激素受体α表达减少（绝经后女性）也可能导致EDD随着年龄的增长而受损。随着年龄的增长，一些生活方式和生物因素会调节血管内皮功能，包括有规律的有氧运动、饮食因素（如加工食品与未加工食品的比较）、体重/肥胖、维生素D状况、更年期/雌激素缺乏以及一些传统和非传统的心血管疾病危险因素。鉴于现在和将来老年人的数量，需要更多的信息来预防和治疗血管内皮老化的有效策略。
Advancing age is the major risk factor for the development of CVD (cardiovascular diseases). This is attributable, in part, to the development of vascular endothelial dysfunction, as indicated by reduced peripheral artery EDD (endothelium-dependent dilation) in response to chemical [typically ACh (acetylcholine)] or mechanical (intravascular shear) stimuli. Reduced bioavailability of the endothelium-synthesized dilating molecule NO (nitric oxide) as a result of oxidative stress is the key mechanism mediating reduced EDD with aging. Vascular oxidative stress increases with age as a consequence of greater production of reactive oxygen species (e.g. superoxide) without a compensatory increase in antioxidant defences. Sources of increased superoxide production include up-regulation of the oxidant enzyme NADPH oxidase, uncoupling of the normally NO-producing enzyme, eNOS (endothelial NO synthase) (due to reduced availability of the cofactor tetrahydrobiopterin) and increased mitochondrial synthesis during oxidative phosphorylation. Increased bioactivity of the potent endothelial-derived constricting factor ET-1 (endothelin-1), reduced endothelial production of/responsiveness to dilatory prostaglandins, the development of vascular inflammation, formation of AGEs (advanced glycation end-products), an increased rate of endothelial apoptosis and reduced expression of oestrogen receptor α (in postmenopausal females) also probably contribute to impaired EDD with aging. Several lifestyle and biological factors modulate vascular endothelial function with aging, including regular aerobic exercise, dietary factors (e.g. processed compared with non-processed foods), body weight/fatness, vitamin D status, menopause/oestrogen deficiency and a number of conventional and non-conventional risk factors for CVD. Given the number of older adults now and in the future, more information is needed on effective strategies for the prevention and treatment of vascular endothelial aging.