title: Vasoprotective effects of resveratrol and SIRT1: attenuation of cigarette smoke-induced oxidative stress and proinflammatory phenotypic alterations.
abstract: 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-kappaB 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 antiaging action in mammals and may be especially beneficial in pathophysiological conditions associated with accelerated vascular aging.
authors.affiliation: Department of Physiology, New York Medical College, Valhalla, NY 10595, USA. anna_csiszar@nymc.edu
authors.forename: Anna
authors.initials: A
authors.lastname: Csiszar
authors.forename: Nazar
authors.initials: N
authors.lastname: Labinskyy
authors.forename: Andrej
authors.initials: A
authors.lastname: Podlutsky
authors.forename: Pawel M
authors.initials: PM
authors.lastname: Kaminski
authors.forename: Michael S
authors.initials: MS
authors.lastname: Wolin
authors.forename: Cuihua
authors.initials: C
authors.lastname: Zhang
authors.forename: Partha
authors.initials: P
authors.lastname: Mukhopadhyay
authors.forename: Pal
authors.initials: P
authors.lastname: Pacher
authors.forename: Furong
authors.initials: F
authors.lastname: Hu
authors.forename: Rafael
authors.initials: R
authors.lastname: de Cabo
authors.forename: Praveen
authors.initials: P
authors.lastname: Ballabh
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Ungvari
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001158:Arteries / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D002339:Carotid Arteries / Q000187:drug effects / Q000201:enzymology; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000187:drug effects / Q000201:enzymology; D019610:Cytoprotection; D004249:DNA Damage / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects / Q000201:enzymology; D007249:Inflammation / Q000201:enzymology / Q000209:etiology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D023421:Models, Animal; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010641:Phenotype; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077185:Resveratrol; D056564:Sirtuin 1; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism*; D012906:Smoke / Q000009:adverse effects*; D012907:Smoking / Q000009:adverse effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D013267:Stilbenes / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D018836:Inflammation Mediators; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D012906:Smoke; D013267:Stilbenes; D014665:Vasodilator Agents; C488368:Sirt1 protein, rat; D056564:Sirtuin 1; D037761:Sirtuins; D000109:Acetylcholine; D000077185:Resveratrol