Vascular Aging: Implications for Cardiovascular Disease and Therapy.
Vascular Aging: Implications for Cardiovascular Disease and Therapy.
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DOI：
10.4172/2161-1025.1000183
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发表时间：
2016-12-01
期刊：
影响因子：
--
通讯作者：
Bonnen, Mark D
中科院分区：
文献类型：
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作者：
Ghebre, Yohannes T;Yakubov, Eduard;Bonnen, Mark D
心血管疾病的发病率和流行率在老年人中最高，部分原因是年龄增长对心脏和血管的有害影响。衰老是已知的心血管危险因素，它与血管的结构和功能变化密切相关，包括氧化应激增加引起的血流动力学紊乱、细胞过早衰老和内皮源性血管活性分子合成和/或分泌障碍。这些分子和生理变化导致血管壁硬化和增厚，以及其他血管并发症，最终导致血管张力调节和内皮功能的丧失。有趣的是，血管壁是一种由胶原蛋白、结缔组织、平滑肌和内皮细胞组成的生物化学活性结构，它受到过早或正常衰老过程的不利影响。值得注意的是，血管壁的最内层，内皮，随着年龄的增长而衰老和功能失调。因此，其释放血管活性分子如乙酰胆碱（ACh）、前列环素（PGI2）、内皮衍生超极化因子（EDHF）和一氧化氮（NO）的能力降低，细胞对这些分子的反应也受到损害。相反，血管内皮增加活性氧（ROS）和活性氮（RNS）的生成和释放，内皮素（ET）和血管紧张素（AT）等血管收缩剂以及内源性NO合成酶抑制剂（nos）的产生和释放。这扭曲了内皮的平衡，有利于释放高组织反应性和有害分子，促进DNA损伤、端粒侵蚀、衰老，以及血管壁硬化，容易导致高血压、糖尿病、动脉粥样硬化和其他心血管危险因素的发生。这篇综述讨论了年龄增长对心血管健康的影响，并强调了年龄相关血管变化的细胞和分子机制。此外，还讨论了药物干预在预防或延缓年龄相关心血管疾病中的作用。
The incidence and prevalence of cardiovascular disease is highest among the elderly, in part, due to deleterious effects of advancing age on the heart and blood vessels. Aging, a known cardiovascular risk factor, is progressively associated with structural and functional changes to the vasculature including hemodynamic disturbance due to increased oxidative stress, premature cellular senescence and impairments in synthesis and/or secretion of endothelium-derived vasoactive molecules. These molecular and physiological changes lead to vessel wall stiffening and thickening, as well as other vascular complications that culminate to loss of vascular tone regulation and endothelial function. Intriguingly, the vessel wall, a biochemically active structure composed of collagen, connective tissue, smooth muscle and endothelial cells, is adversely affected by processes involved in premature or normal aging. Notably, the inner most layer of the vessel wall, the endothelium, becomes senescent and dysfunctional with advancing age. As a result, its ability to release vasoactive molecules such as acetylcholine (ACh), prostacyclin (PGI2), endothelium-derived hyperpolarizing factor (EDHF), and nitric oxide (NO) is reduced and the cellular response to these molecules is also impaired. By contrast, the vascular endothelium increases its generation and release of reactive oxygen (ROS) and nitrogen (RNS) species, vasoconstrictors such as endothelin (ET) and angiotensin (AT), and endogenous inhibitors of NO synthases (NOSs) to block NO. This skews the balance of the endothelium in favor of the release of highly tissue reactive and harmful molecules that promote DNA damage, telomere erosion, senescence, as well as stiffened and hardened vessel wall that is prone to the development of hypertension, diabetes, atherosclerosis and other cardiovascular risk factors. This Review discusses the impact of advancing age on cardiovascular health, and highlights the cellular and molecular mechanisms that underlie age-associated vascular changes. In addition, the role of pharmacological interventions in preventing or delaying age-related cardiovascular disease is discussed.