Schmitt Christoph A, Handler Norbert, Heiss Elke H, Erker Thomas, Dirsch Verena M
Department of Pharmacognosy, University of Vienna, A-1090 Vienna, Austria.
Atherosclerosis. 2007 Nov;195(1):e58-64. doi: 10.1016/j.atherosclerosis.2007.02.024. Epub 2007 Mar 30.
Reduced nitric oxide (NO) availability is associated with the development of atherosclerosis. Upregulation of endothelial nitric oxide synthase (eNOS) activity is pursued as a strategy for the prevention of cardiovascular diseases. The polyphenol hydroxytyrosol (HT) which is present in olive oil and red wine, is regarded to be partly responsible for the beneficial effects associated with olive oil consumption and has shown antiatherogenic activity in vitro and in vivo. To elucidate the underlying molecular mechanisms, we investigated possible effects of HT on the endothelial nitric oxide synthase (eNOS). We used human endothelial cells (EA.hy926) and examined eNOS on three different levels, addressing eNOS promoter transactivation, eNOS enzyme activity and nitric oxide availability. Cells were treated with a broad range of HT concentrations (from 10 nM to 100 microM) and for different incubation times (15 min to 24 h). HT did not exert significant positive effects on eNOS in any of our assay systems. Neither did we find evidence for a possible synergism between the red wine polyphenol resveratrol and HT. We conclude that a direct modulation of eNOS is unlikely to account for the antiatherogenic properties of HT under non-inflammatory conditions.
一氧化氮（NO）可用性降低与动脉粥样硬化的发展有关。上调内皮型一氧化氮合酶（eNOS）活性是预防心血管疾病的一种策略。存在于橄榄油和红酒中的多酚羟基酪醇（HT），被认为是橄榄油消费带来有益影响的部分原因，并且在体外和体内均显示出抗动脉粥样硬化活性。为了阐明潜在的分子机制，我们研究了HT对内皮型一氧化氮合酶（eNOS）的可能影响。我们使用人内皮细胞（EA.hy926）并在三个不同水平上检测eNOS，涉及eNOS启动子反式激活、eNOS酶活性和一氧化氮可用性。用广泛范围的HT浓度（从10 nM到100 microM）处理细胞，并进行不同的孵育时间（15分钟到24小时）。在我们的任何检测系统中，HT对eNOS均未产生显著的积极作用。我们也未发现红酒多酚白藜芦醇与HT之间可能存在协同作用的证据。我们得出结论，在非炎症条件下，eNOS的直接调节不太可能解释HT的抗动脉粥样硬化特性。
