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Vasoprotective effects of resveratrol and SIRT1: attenuation of cigarette smoke-induced oxidative stress and proinflammatory phenotypic alterations
Ist Teil von
American journal of physiology. Heart and circulatory physiology, 2008-06, Vol.294 (6), p.H2721-H2735
Ort / Verlag
United States: American Physiological Society
Erscheinungsjahr
2008
Link zum Volltext
Quelle
Electronic Journals Library
Beschreibungen/Notizen
Departments of 1 Physiology and 2 Cell Biology, New York Medical College, Valhalla, New York; 3 The Sam and Ann Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center, San Antonio, Texas; 4 Departments of Internal Medicine and Medical Pharmacology and Physiology, Dalton Cardiovascular Research Center, University of Missouri-Columbia, Columbia, Missouri; 5 Section on Oxidative Stress Tissue Injury, Laboratory of Physiological Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda; and 6 Laboratory of Experimental Gerontology, National Institute on Aging, Baltimore, Maryland
Submitted 4 March 2008
; accepted in final form 15 April 2008
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- ) in rat arteries was also abrogated by resveratrol treatment. Resveratrol also inhibited CSE-induced NF- 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 antiaging action in mammals and may be especially beneficial in pathophysiological conditions associated with accelerated vascular aging.
tobacco; polyphenol; stroke; inflammation; apoptosis; vascular aging; sirtuin 1
Address for reprint requests and other correspondence: Z. Ungvari or A. Csiszar, Dept. of Physiology, New York Medical College, Valhalla, NY 10595 (e-mail: zoltan_ungvari{at}nymc.edu )