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.
Red wine extract protects against oxidative-stress-induced endothelial senescence
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Ilse P. G. Botden, Hisko Oeseburg, Matej Durik, Frank P. J. Leijten, Leonie C. Van Vark-Van Der Zee, Usha M. Musterd-Bhaggoe, Ingrid M. Garrelds, Ann L. B. Seynhaeve, Janneke G. Langendonk, Eric J. G. Sijbrands, A. H. Jan Danser, Anton J. M. Roks; Red wine extract protects against oxidative-stress-induced endothelial senescence. Clin Sci (Lond) 1 October 2012; 123 (8): 499–507. doi: https://doi.org/10.1042/CS20110679
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