Vascular protection by dietary polyphenols
Abstract
Consumption of polyphenol-rich foods, such as fruits and vegetables, and beverages derived from plants, such as cocoa, red wine and tea, may represent a beneficial diet in terms of cardiovascular protection. Indeed, epidemiological studies demonstrate a significant inverse correlation between polyphenol consumption and cardiovascular risk. Among the numerous plausible mechanisms by which polyphenols may confer cardiovascular protection, improvement of the endothelial function and inhibition of angiogenesis and cell migration and proliferation in blood vessels have been the focus of recent studies. These studies have indicated that, in addition to and independently from their antioxidant effects, plant polyphenols (1) enhance the production of vasodilating factors [nitric oxide (NO), endothelium-derived hyperpolarizing factor (EDHF) and prostacyclin] and inhibit the synthesis of vasoconstrictor endothelin-1 in endothelial cells; and (2) inhibit the expression of two major pro-angiogenic factors, vascular endothelial growth factor (VEGF) and matrix metalloproteinase-2 (MMP-2) in smooth muscle cells. The mechanisms of these effects involve: (1) in endothelial cells, increased Ca2+ level and redox-sensitive activation of the phosphoinositide 3 (PI3)-kinase/Akt pathway (leading to rapid and sustained activation of nitric oxide synthase and formation of EDHF) and enhanced expression of nitric oxide synthase; and (2) in smooth muscle cells, both redox-sensitive inhibition of the p38 mitogen-activated protein kinase (p38 MAPK) pathway activation (leading to inhibition of platelet-derived growth factor (PDGF)-induced VEGF gene expression) and redox-insensitive mechanisms (leading to inhibition of thrombin-induced MMP-2 formation). The current evidence suggests that all these mechanisms are triggered by polyphenols with specific structures, although the structural requirements may be different from one effect to the other, and that they all contribute to the vasoprotective, anti-angiogenic, anti-atherogenic, vasorelaxant and anti-hypertensive effects of acute or chronic administration of plant polyphenols found in vivo in animals and in patients.
食用富含多酚的食物，如水果和蔬菜，以及从植物中提取的饮料，如可可、红酒和茶，在心血管保护方面可能是有益的饮食。事实上，流行病学研究表明多酚消费与心血管风险之间存在显著的负相关关系。在众多可能的机制中，多酚可能提供心血管保护，改善内皮功能和抑制血管生成、细胞迁移和血管增殖已成为最近的研究重点。这些研究表明，除了抗氧化作用外，植物多酚(1)可增强血管舒张因子[一氧化氮(NO)、内皮衍生超极化因子(EDHF)和前列环素]的产生，并抑制内皮素-1在内皮细胞中的合成;(2)抑制两种主要促血管生成因子血管内皮生长因子(VEGF)和基质金属蛋白酶-2 (MMP-2)在平滑肌细胞中的表达。这些作用的机制包括:(1)在内皮细胞中，Ca2+水平升高，磷酸肌苷3 (PI3)-激酶/Akt通路氧化还原敏感激活(导致一氧化氮合酶快速持续激活和EDHF形成)，一氧化氮合酶表达增强;和(2)在平滑肌细胞redox-sensitive p38增殖的抑制蛋白激酶(p38 MAPK)途径激活(导致抑制血小板源生长因子(PDGF)全身的VEGF基因表达)和redox-insensitive机制(导致抑制thrombin-induced MMP-2形成)。目前的证据表明，所有这些机制都是由具有特定结构的多酚触发的，尽管结构需求可能因一种效应而不同，而且它们都有助于血管保护、抗血管生成、抗动脉粥样硬化，在动物和病人体内发现的植物多酚急性或慢性给药的血管松弛剂和抗高血压作用。
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https://www.sciencedirect.com/science/article/abs/pii/S0014299904007435
