title: Physiological concentrations of dietary polyphenols regulate vascular endothelial cell expression of genes important in cardiovascular health.
abstract: Previous cell culture-based studies have shown potential health beneficial effects on gene expression of dietary polyphenols, including those found in red wine and green tea. However, these studies have tended to use higher concentrations (2-100 microm) than those observed in blood (0.1-1 microm) after consuming polyphenol-rich foods or beverages. The present study investigated effects of physiological concentrations of different classes of dietary polyphenol on the expression of genes important in cardiovascular health (endothelial NO synthase (eNOS), endothelin-1 (ET-1) and vascular endothelial growth factor (VEGF)) by cultured vascular endothelial cells (human umbilical vein endothelial cells) in the absence or presence of H2O2. Resveratrol and quercetin (0.1-1 microm) increased eNOS and VEGF mRNA expression particularly in the absence of H2O2 (50 microm) and decreased H2O2-induced ET-1 mRNA expression (P < 0.001 for polyphenol x H2O2 interactions). Similarly, resveratrol and quercetin decreased endothelin secretion into the media, blocking the stimulatory effect of 50 microm-H2O2 (P < 0.001 for polyphenol x H2O2 interaction). Of the nine other polyphenols tested, only epigallocatechin gallate had similar effects on both the eNOS and ET-1 mRNA expression, but to a lesser extent than resveratrol at an equimolar concentration (0.1 microm). The observed effects on gene expression would be expected to result in vasodilation and thereby reduced blood pressure. Since only three of the eleven polyphenols tested had biological activity, it is unclear whether particular structures are important or whether the effects might relate to the relatively high antioxidant capacities of the three active polyphenols.
authors.affiliation: Division of Nutritional Sciences, School of Biosciences, University of Nottingham, Sutton Bonington Campus, Loughborough, Leics LE12 5RD, UK.
authors.forename: Sonja K
authors.initials: SK
authors.lastname: Nicholson
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Tucker
authors.forename: John M
authors.initials: JM
authors.lastname: Brameld
mesh_terms: D002478:Cells, Cultured; D004032:Diet; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects*; D019332:Endothelin-1 / Q000235:genetics / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D006861:Hydrogen Peroxide; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D010636:Phenols / Q000494:pharmacology; D059808:Polyphenols; D011794:Quercetin / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D019332:Endothelin-1; D005419:Flavonoids; D010636:Phenols; D059808:Polyphenols; D012333:RNA, Messenger; D013267:Stilbenes; D011794:Quercetin; D006861:Hydrogen Peroxide; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D000077185:Resveratrol