Red wine extract protects against oxidative-stress-induced endothelial senescence

Ilse Botden, Hisko Oeseburg, Matej Durik, FRJ Leijten, LC van Vark-van de Zee, UM Musterd-Bhaggoe, Ingrid Van den Berg - Garrelds, Ann Seynhaeve, Janneke Langendonk, E.J.G. Sijbrands, Jan Danser, Anton Roks

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23 Citations (Scopus)

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 beta-galactosidase staining. RWE (0-50 mu g/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 (N-G-monomethyl-L-arginine) and the COX (cyclooxygenase) 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 Ser(1177). 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.
Original languageUndefined/Unknown
Pages (from-to)499-507
Number of pages9
JournalClinical Science
Volume123
Issue number7-8
DOIs
Publication statusPublished - 2012

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