title: Red wine extract protects against oxidative-stress-induced endothelial senescence.
abstract: Red wine polyphenols may preserve endothelial function during aging. Endothelial cell senescence enhances age-related endothelial dysfunction. We investigated whether RWE (red wine extract) prevents oxidative-stress-induced senescence in HUVECs (human umbilical-vein endothelial cells). Senescence was induced by exposing HUVECs to tBHP (t-butylhydroperoxide), and quantified by senescence-associated β-galactosidase staining. RWE (0-50 μg/ml) concentration dependently decreased senescence by maximally 33±7.1%. RWE prevented the senescence-associated increase in p21 protein expression, inhibited tBHP-induced DNA damage of endothelial cells and induced relaxation of PCAs (porcine coronary arteries). Inhibition of SIRT1 (sirtuin 1) by sirtinol partially reversed the effect of RWE on tBHP-induced senescence, whereas both the NOS (nitric oxide synthase) inhibitor L-NMMA (NG-monomethyl-L-arginine) and the COX (cyclo-oxygenase) inhibitor indomethacin fully inhibited it. Furthermore, incubation of HUVECs with RWE increased eNOS (endothelial NOS) and COX-2 mRNA levels as well as phosphorylation of eNOS at Ser1177. RWE protects endothelial cells from tBHP-induced senescence. NO and COX-2, in addition to activation of SIRT1, play a critical role in the inhibition of senescence induction in human endothelial cells by RWE.
authors.affiliation: Department of Internal Medicine, Division of Vascular Medicine and Pharmacology, Erasmus University Medical Center, Dr Molewaterplein 50-60, 3015 GE, Rotterdam, The Netherlands.
authors.forename: Ilse P G
authors.initials: IP
authors.lastname: Botden
authors.forename: Hisko
authors.initials: H
authors.lastname: Oeseburg
authors.forename: Matej
authors.initials: M
authors.lastname: Durik
authors.forename: Frank P J
authors.initials: FP
authors.lastname: Leijten
authors.forename: Leonie C
authors.initials: LC
authors.lastname: Van Vark-Van Der Zee
authors.forename: Usha M
authors.initials: UM
authors.lastname: Musterd-Bhaggoe
authors.forename: Ingrid M
authors.initials: IM
authors.lastname: Garrelds
authors.forename: Ann L B
authors.initials: AL
authors.lastname: Seynhaeve
authors.forename: Janneke G
authors.initials: JG
authors.lastname: Langendonk
authors.forename: Eric J G
authors.initials: EJ
authors.lastname: Sijbrands
authors.forename: A H Jan
authors.initials: AH
authors.lastname: Danser
authors.forename: Anton J M
authors.initials: AJ
authors.lastname: Roks
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects* / Q000502:physiology; D004249:DNA Damage / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D010936:Plant Extracts / Q000494:pharmacology; D059808:Polyphenols / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism; D000077185:Resveratrol; D056564:Sirtuin 1 / Q000502:physiology; D013267:Stilbenes / Q000494:pharmacology; D014920:Wine / Q000032:analysis*; D001616:beta-Galactosidase / Q000378:metabolism; D020122:tert-Butylhydroperoxide / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D010936:Plant Extracts; D059808:Polyphenols; D011453:Prostaglandins; D013267:Stilbenes; D020122:tert-Butylhydroperoxide; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D001616:beta-Galactosidase; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D000077185:Resveratrol