Vasoprotective effects of resveratrol and SIRT1: attenuation of cigarette smoke-induced oxidative stress and proinflammatory phenotypic alterations
Vasoprotective effects of resveratrol and SIRT1: attenuation of cigarette smoke-induced oxidative stress and proinflammatory phenotypic alterations
复制标题
DOI：
10.1152/ajpheart.00235.2008
复制
发表时间：
2008-06-01
影响因子：
4.8
通讯作者：
Ungvari, Zoltan
中科院分区：
文献类型：
--
作者：
Csiszar, Anna;Labinskyy, Nazar;Ungvari, Zoltan
膳食多酚化合物白藜芦醇通过激活蛋白质脱乙酰酶沉默信息调节因子 2/sirtuin 1 (SIRT1)，延长进化遥远的生物体的寿命，并可能模仿饮食限制的细胞保护作用。本研究旨在阐明白藜芦醇对香烟烟雾引起的血管氧化应激和炎症的影响，这是临床上高度相关的加速血管老化模型。老鼠暴露于香烟烟雾会损害乙酰胆碱引起的颈动脉松弛，这可以通过白藜芦醇治疗来预防。吸烟和香烟烟雾提取物（CSE）体外处理分别增加了大鼠动脉和培养的冠状动脉内皮细胞（CAEC）中活性氧的产生，而白藜芦醇处理则减弱了活性氧的产生。白藜芦醇治疗也消除了吸烟引起的大鼠动脉炎症标志物（ICAM-1、诱导型一氧化氮合酶、IL-6 和 TNF-α）的上调。白藜芦醇还抑制 CSE 诱导的 CAEC 中 NF-κ B 激活和炎症基因表达。在CAEC中，敲除SIRT1可以消除白藜芦醇的上述保护作用，而SIRT1的过度表达则模仿了白藜芦醇的作用。白藜芦醇治疗大鼠可保护主动脉内皮细胞免受吸烟引起的细胞凋亡。白藜芦醇还在 CSE 处理的 CAEC 中发挥抗凋亡作用，这种作用可以通过敲低 SIRT1 来消除。白藜芦醇治疗还可以减轻 CSE 诱导的 CAEC 中的 DNA 损伤（彗星测定）。因此，白藜芦醇和 SIRT1 发挥抗氧化、抗炎和抗凋亡作用，保护内皮细胞免受吸烟引起的氧化应激的不利影响。白藜芦醇的血管保护作用可能有助于其在哺乳动物中的抗衰老作用，并且可能对与血管加速衰老相关的病理生理状况特别有益。
The dietary polyphenolic compound resveratrol, by activating the protein deacetylase enzyme silent information regulator 2/sirtuin 1 (SIRT1), prolongs life span in evolutionarily distant organisms and may mimic the cytoprotective effects of dietary restriction. The present study was designed to elucidate the effects of resveratrol on cigarette smoke-induced vascular oxidative stress and inflammation, which is a clinically highly relevant model of accelerated vascular aging. Cigarette smoke exposure of rats impaired the acetylcholine-induced relaxation of carotid arteries, which could be prevented by resveratrol treatment. Smoking and in vitro treatment with cigarette smoke extract (CSE) increased reactive oxygen species production in rat arteries and cultured coronary arterial endothelial cells (CAECs), respectively, which was attenuated by resveratrol treatment. The smoking-induced upregulation of inflammatory markers (ICAM-1, inducible nitric oxide synthase, IL-6, and TNF-alpha) in rat arteries was also abrogated by resveratrol treatment. Resveratrol also inhibited CSE-induced NF-kappa B activation and inflammatory gene expression in CAECs. In CAECs, the aforementioned protective effects of resveratrol were abolished by knockdown of SIRT1, whereas the overexpression of SIRT1 mimicked the effects of resveratrol. Resveratrol treatment of rats protected aortic endothelial cells against cigarette smoking-induced apoptotic cell death. Resveratrol also exerted antiapoptotic effects in CSE-treated CAECs, which could be abrogated by knockdown of SIRT1. Resveratrol treatment also attenuated CSE-induced DNA damage in CAECs (comet assay). Thus resveratrol and SIRT1 exert antioxidant, anti-inflammatory, and antiapoptotic effects, which protect the endothelial cells against the adverse effects of cigarette smoking-induced oxidative stress. The vasoprotective effects of resveratrol will likely contribute to its anti-aging action in mammals and may be especially beneficial in pathophysiological conditions associated with accelerated vascular aging.