Red wine polyphenols enhance endothelial nitric oxide synthase expression and subsequent nitric oxide release from endothelial cells
Red wine polyphenols enhance endothelial nitric oxide synthase expression and subsequent nitric oxide release from endothelial cells
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DOI：
10.1161/01.cir.0000034445.31543.43
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发表时间：
2002-09-24
期刊：
影响因子：
37.8
通讯作者：
Dirsch, VM
中科院分区：
文献类型：
--
作者：
Leikert, JF;Räthel, TR;Dirsch, VM
背景-基于人群的研究表明，适量和经常饮用红酒可降低冠心病的发病率和死亡率。内皮细胞一氧化氮（NO）是一种重要的血管保护分子。本研究检测了红葡萄酒多酚对内皮型一氧化氮合酶（eNOS）表达和随后NO合成的调节的影响，研究重点是红葡萄酒的持久抗动脉粥样硬化作用。人脐静脉内皮细胞（HUVEC）和HUVEC衍生的细胞系EA.hy926与无醇红葡萄酒多酚提取物（RWPE）导致NO释放的浓度依赖性（100至600 μ g/mL）显著增加（高达3.0倍/HUVEC和2.0倍/EA.hy926），如通过使用荧光探针FITC-2所示。在完整EA.hy926细胞中进行的[C-14] L-精氨酸/L-瓜氨酸转化试验证实了该效应。RWPE（20小时，100至600 μ g/mL）也显着增加eNOS蛋白水平高达2.1倍。此外，我们发现增加的人eNOS proinotor活性（高达2倍），在响应红葡萄酒多酚（18小时，100至600所证明的荧光素酶报告基因assay. Conclusion，我们提供了确凿的数据表明，第一次，RWPE增加eNOS表达和随后的内皮NO释放。活性eNOS水平的增加可能会拮抗内皮功能障碍和动脉粥样硬化的发展，这一假设支持了红葡萄酒确实可能具有由其多酚介导的长期保护心血管特性的观点。
Background-Population-based studies suggest a reduced incidence of morbidity and mortality from coronary heart disease caused by moderate and regular consumption of red wine. Enclothelial nitric oxide (NO) is a pivotal vasoprotective molecule. This study examines the influence of red wine polyphenols on the regulation of endothelial nitric oxide synthase (eNOS) expression and subsequent NO synthesis, focusing on the putative long-lasting antiatherosclerotic effects of red wine.Methods and Results-Treatment (20 hours) of human umbilical vein endothelial cells (HUVECs) and of the HUVEC-derived cell line EA.hy926 with a alcohol-free red wine polyphenol extract (RWPE) led to a concentration-dependent (100 to 600 mug/mL), significant increase in NO release (up to 3.0-fold/HUVEC and 2.0-fold/EA.hy926) as shown by use of the fluorescent probe DAF-2. This effect was corroborated by the [C-14]L-arginine/L-citrulline conversion assay in intact EA.hy926 cells. RWPE (20 hours, 100 to 600 mug/mL) also significantly increased eNOS protein levels up to 2.1-fold. Furthermore, we found an increased human eNOS proinotor activity (up to 2-fold) in response to red wine polyphenols (18 hours, 100 to 600 as demonstrated by a luciferase reporter gene assay.Conclusion-We provide conclusive data showing for the first time that a RWPE increases eNOS expression and subsequent endothelial NO release. Increased active eNOS levels may antagonize the development of endothelial dysfunction and atherosclerosis, a hypothesis that supports the view that red wine indeed may have long-term protective cardiovascular properties mediated by its polyphenols.