Resveratrol Improves Vascular Function in Patients With Hypertension and Dyslipidemia by Modulating NO Metabolism
Resveratrol Improves Vascular Function in Patients With Hypertension and Dyslipidemia by Modulating NO Metabolism
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DOI：
10.1161/hypertensionaha.111.01009
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发表时间：
2013-08-01
期刊：
影响因子：
8.3
通讯作者：
Vecchione, Carmine
中科院分区：
文献类型：
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作者：
Carrizzo, Albino;Puca, Annibale;Vecchione, Carmine
流行病学研究表明，富含白藜芦醇的地中海饮食与显著降低心血管疾病风险有关。然而，白藜芦醇对心血管功能有益作用的分子机制仍不完全清楚。因此，我们着手确定介导白藜芦醇对血管功能保护作用的分子靶点。为此，我们进行了血管反应性研究，以评估白藜芦醇对上级甲状腺动脉的影响，从59例高血压和血脂异常患者。我们发现白藜芦醇通过调节NO代谢引起血管舒张并减少内皮功能障碍，其途径是：（1）5-腺苷一磷酸活化蛋白激酶介导的内皮NO合成酶活性的增加;（2）四氢生物蝶呤水平的升高，这也增加了内皮NO合成酶活性;和（3）通过核因子红细胞衍生的2-样2-依赖性机制，锰超氧化物歧化酶过表达引起的血管氧化应激的减弱。白藜芦醇对乙酰胆碱血管舒张的影响也在接受甲状腺手术的非高血压非血脂异常患者的血管中进行了测试。在这种情况下，白藜芦醇未能发挥任何作用。因此，我们发现白藜芦醇可以减少内皮功能障碍，这是大多数心血管疾病的早期病理生理学特征和预后不良的独立预测因子，支持了血管事件风险可以通过遵守一套饮食和行为指南进一步降低的概念。
Epidemiological studies have demonstrated that the Mediterranean diet, which is rich in resveratrol, is associated with a significantly reduced risk of cardiovascular disease. However, the molecular mechanisms that underlie the beneficial effects of resveratrol on cardiovascular function remain incompletely understood. Therefore, we set out to identify the molecular target(s) mediating the protective action of resveratrol on vascular function. To this end, we performed vascular reactivity studies to evaluate the effects of resveratrol on superior thyroid artery obtained from 59 patients with hypertension and dyslipidemia. We found that resveratrol evoked vasorelaxation and reduced endothelial dysfunction through the modulation of NO metabolism via (1) an 5 adenosine monophosphate-activated protein kinase-mediated increase in endothelial NO synthase activity; (2) a rise in tetrahydrobiopterin levels, which also increases endothelial NO synthase activity; and (3) attenuation of vascular oxidative stress, brought about by overexpression of manganese superoxide dismutase via an nuclear factor erythroid-derived 2-like 2-dependent mechanism. The effects of resveratrol on acetylcholine vasorelaxation were also tested in vessels from patients with nonhypertensive nondyslipidemia undergoing thyroid surgery. In this setting, resveratrol failed to exert any effect. Thus, our finding that resveratrol reduces endothelial dysfunction, an early pathophysiological feature and independent predictor of poor prognosis in most forms of cardiovascular disease, supports the concept that the risk of vascular events could be further reduced by adherence to a set of dietary and behavioral guidelines.