The protective role of Sirt1 in vascular tissue: its relationship to vascular aging and atherosclerosis.
The protective role of Sirt1 in vascular tissue: its relationship to vascular aging and atherosclerosis.
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DOI：
10.18632/aging.101068
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发表时间：
2016-10-15
期刊：
影响因子：
--
通讯作者：
Koya D
中科院分区：
文献类型：
--
作者：
Kitada M;Ogura Y;Koya D
动脉粥样硬化引起的心血管疾病（CVD）是老年人和代谢性疾病（包括糖尿病）患者死亡的主要原因。衰老过程有助于动脉粥样硬化的发病机制。热量限制（CR）被认为是促进长寿和延缓年龄相关疾病（包括动脉粥样硬化）的饮食干预措施。Sirt 1是一种NAD+依赖性脱乙酰酶，被认为是一种抗衰老分子，在CR期间被诱导。Sirt 1使靶蛋白去乙酰化，并与细胞代谢、氧化还原状态和存活途径有关。Sirt 1表达/激活在经历衰老的血管组织中减少。内皮细胞（EC）、血管平滑肌细胞（VSMC）和单核细胞/巨噬细胞中的Sirt 1缺陷有助于增加氧化应激、炎症、泡沫细胞形成、衰老受损的一氧化氮产生和自噬，从而促进血管老化和动脉粥样硬化。内皮功能障碍、单核细胞/巨噬细胞的活化以及VSMC的功能和表型可塑性通过多种机制与动脉粥样硬化的发病机制密切相关。因此，Sirt 1在血管组织，包括EC，单核细胞/巨噬细胞和VSMCs中的激活，可能是一种新的治疗策略，用于对抗动脉粥样硬化和增加对CVD的代谢紊乱相关致病因素的抵抗力。在这篇综述中，我们讨论了Sirt 1在血管老化和动脉粥样硬化的病理生理学中的保护作用。
Cardiovascular disease (CVD) due to atherosclerosis is the main cause of death in both the elderly and patients with metabolic diseases, including diabetes. Aging processes contribute to the pathogenesis of atherosclerosis. Calorie restriction (CR) is recognized as a dietary intervention for promoting longevity and delaying age-related diseases, including atherosclerosis. Sirt1, an NAD+-dependent deacetylase, is considered an anti-aging molecule and is induced during CR. Sirt1 deacetylates target proteins and is linked to cellular metabolism, the redox state and survival pathways. Sirt1 expression/activation is decreased in vascular tissue undergoing senescence. Sirt1 deficiency in endothelial cells (ECs), vascular smooth muscle cells (VSMCs) and monocytes/macrophages contributes to increased oxidative stress, inflammation, foam cell formation, senescences impaired nitric oxide production and autophagy, thereby promoting vascular aging and atherosclerosis. Endothelial dysfunction, activation of monocytes/macrophages, and the functional and phenotypical plasticity of VSMCs are critically implicated in the pathogenesis of atherosclerosis through multiple mechanisms. Therefore, the activation of Sirt1 in vascular tissue, which includes ECs, monocytes/macrophages and VSMCs, may be a new therapeutic strategy against atherosclerosis and the increasing resistance to the metabolic disorder-related causal factors of CVD. In this review, we discuss the protective role of Sirt1 in the pathophysiology of vascular aging and atherosclerosis.
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DOI：
10.1126/science.1173635
发表时间：
2009-07-10
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Colman RJ;Anderson RM;Johnson SC;Kastman EK;Kosmatka KJ;Beasley TM;Allison DB;Cruzen C;Simmons HA;Kemnitz JW;Weindruch R
通讯作者：
Weindruch R
影响因子：
--
作者：
Bai B;Man AW;Yang K;Guo Y;Xu C;Tse HF;Han W;Bloksgaard M;De Mey JG;Vanhoutte PM;Xu A;Wang Y
通讯作者：
Wang Y
影响因子：
7.3
作者：
Arunachalam G;Samuel SM;Marei I;Ding H;Triggle CR
通讯作者：
Triggle CR
影响因子：
4.8
作者：
Chen, J;Zhou, YG;Li, G
通讯作者：
Li, G
影响因子：
5
作者：
Donato AJ;Morgan RG;Walker AE;Lesniewski LA
通讯作者：
Lesniewski LA