Department of Internal Medicine, Division of Vascular Medicine and Pharmacology, Erasmus University Medical Center, Dr Molewaterplein 50-60, 3015 GE, Rotterdam, The Netherlands.
Clin Sci (Lond). 2012 Oct;123(8):499-507. doi: 10.1042/CS20110679.
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.
红酒多酚可在衰老过程中保护内皮功能。内皮细胞衰老增强了与年龄相关的内皮功能障碍。我们研究了 RWE（红酒提取物）是否可以预防 HUVEC（人脐静脉内皮细胞）中氧化应激诱导的衰老。通过用 tBHP（叔丁基过氧化物）处理 HUVEC 来诱导衰老，并通过衰老相关的β-半乳糖苷酶染色来定量。RWE（0-50μg/ml）浓度依赖性地将衰老最大减少 33±7.1%。RWE 可预防衰老相关的 p21 蛋白表达增加，抑制内皮细胞中 tBHP 诱导的 DNA 损伤，并诱导 PCAs（猪冠状动脉）松弛。用 sirtinol 抑制 SIRT1（沉默调节蛋白 1）部分逆转了 RWE 对 tBHP 诱导的衰老的作用，而一氧化氮合酶（NOS）抑制剂 L-NMMA（NG-单甲基-L-精氨酸）和环氧化酶（COX）抑制剂吲哚美辛则完全抑制了它。此外，用 RWE 孵育 HUVEC 可增加 eNOS（内皮型一氧化氮合酶）和 COX-2 mRNA 水平以及 eNOS 在 Ser1177 处的磷酸化。RWE 可保护内皮细胞免受 tBHP 诱导的衰老。NO 和 COX-2 以及 SIRT1 的激活在 RWE 抑制人内皮细胞衰老诱导中起关键作用。
