title: Activation of endothelial nitric oxide synthase by dietary isoflavones: role of NO in Nrf2-mediated antioxidant gene expression.
abstract: The endothelium plays a key role in the maintenance of vascular homeostasis, and increased oxidative stress in vascular disease leads to reduced nitric oxide bioavailability and impaired endothelium-dependent relaxation of resistance vessels. Although epidemiological evidence suggests that diets containing high amounts of natural antioxidants afford protection against coronary heart disease (CHD), antioxidant supplementation trials have largely reported only marginal health benefits. There is controversy concerning the cardiovascular benefits of prolonged estrogen/progestin or soy isoflavone therapy for postmenopausal women and patients with an increased risk of CHD. Research on the potential health benefits of soy isoflavones and other polyphenols contained in red wine, green and black tea and dark chocolate developed rapidly during the 1990's, and recent clinical trials and studies in animal models and cultured endothelial cells provide important and novel insights into the mechanisms by which dietary polyphenols afford protection against oxidative stress. In this review, we highlight that NO and reactive oxygen radicals may mediate dietary polyphenol induced activation of Nrf2, which in turn triggers antioxidant response element (ARE) driven transcription of phase II detoxifying and antioxidant defense enzymes in vascular cells.
authors.affiliation: Cardiovascular Division, School of Medicine, King's College London, 150 Stamford Street, London SE1 9NH, UK. giovanni.mann@kcl.ac.uk
authors.forename: Giovanni E
authors.initials: GE
authors.lastname: Mann
authors.forename: David J
authors.initials: DJ
authors.lastname: Rowlands
authors.forename: Francois Y L
authors.initials: FY
authors.lastname: Li
authors.forename: Patricia
authors.initials: P
authors.lastname: de Winter
authors.forename: Richard C M
authors.initials: RC
authors.lastname: Siow
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D004032:Diet; D004730:Endothelium, Vascular / Q000378:metabolism*; D004789:Enzyme Activation; D015870:Gene Expression; D006801:Humans; D007529:Isoflavones / Q000378:metabolism*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D020218:Response Elements
chemical_list: D000975:Antioxidants; D007529:Isoflavones; D051267:NF-E2-Related Factor 2; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III