Nicholson Sonja K, Tucker Gregory A, Brameld John M
Division of Nutritional Sciences, University of Nottingham, School of Biosciences, Loughborough LE12 5RD, UK.
Proc Nutr Soc. 2008 Feb;67(1):42-7. doi: 10.1017/S0029665108006009.
Previous studies have shown that consumption of fruit and vegetables plays a role in preventing the onset of CVD. These beneficial effects have been linked to the presence of polyphenolic compounds in plant-derived foods and their antioxidant capacity. It has been hypothesised that polyphenols may also have a direct effect on vascular endothelial cell growth and the expression of genes involved in angiogenesis and other roles of the endothelium. Previous studies in this area have tended to use concentrations of polyphenols that are supraphysiological (1-100 microm). The effects of more physiological concentrations (0.1 microm) of various individual polyphenols on gene expression were therefore investigated in cultured human umbilical vein endothelial cells (HUVEC) using both microarray and quantitative RT-PCR methodologies. Treatment of HUVEC with ferulic acid, quercetin or resveratrol (0.1 microm) resulted in changes to gene expression that for the three treatments amounted to significant (>2-fold) down-regulation of the expression of 363 genes and significant (>2-fold) up-regulation of 233 genes of the 10 000 genes present on the microarray. The majority of these genes were affected by resveratrol. Quantitative RT-PCR studies indicated that resveratrol (0.1 microm) significantly increased the expression of the gene encoding endothelial NO synthase (eNOS), which synthesises the vasodilator molecule NO, and both resveratrol and quercetin decreased expression of the potent vasoconstrictor, endothelin-1 (ET-1), while ferulic acid had no effect. The effects of resveratrol (0.1 microm) were also investigated when HUVEC were under oxidative stress following treatment with H2O2 (0-50 microm), which dose-dependently increased expression of eNOS and ET-1. Resveratrol stimulated eNOS mRNA in the absence of H2O2 and still allowed the increase with H2O2, but the effects were not additive. In contrast, resveratrol blocked the stimulatory effect of H2O2 on ET-1 expression. Hence, resveratrol has potent effects at a physiological concentration (0.1 microm) that would be expected to result in vasodilation and therefore help reduce blood pressure and the risk of CVD.
先前的研究表明，食用水果和蔬菜在预防心血管疾病（CVD）的发病中发挥作用。这些有益作用与植物性食物中多酚类化合物的存在及其抗氧化能力有关。据推测，多酚类物质可能还对血管内皮细胞生长以及参与血管生成和内皮细胞其他功能的基因表达有直接影响。该领域先前的研究往往使用超生理浓度（1 - 100微摩尔）的多酚类物质。因此，采用微阵列和定量逆转录聚合酶链反应（RT - PCR）方法，研究了更接近生理浓度（0.1微摩尔）的各种单个多酚类物质对培养的人脐静脉内皮细胞（HUVEC）基因表达的影响。用阿魏酸、槲皮素或白藜芦醇（0.1微摩尔）处理HUVEC后，基因表达发生了变化，在微阵列上的10000个基因中，这三种处理导致363个基因的表达显著下调（>2倍），233个基因的表达显著上调（>2倍）。这些基因中的大多数受白藜芦醇影响。定量RT - PCR研究表明，白藜芦醇（0.1微摩尔）显著增加了编码内皮型一氧化氮合酶（eNOS）的基因表达，eNOS可合成血管舒张分子一氧化氮（NO），白藜芦醇和槲皮素均降低了强效血管收缩剂内皮素 - 1（ET - 1）的表达，而阿魏酸没有影响。在用过氧化氢（0 - 50微摩尔）处理使HUVEC处于氧化应激状态时，也研究了白藜芦醇（0.1微摩尔）的作用，过氧化氢剂量依赖性地增加了eNOS和ET - 1的表达。白藜芦醇在无过氧化氢时刺激eNOS mRNA表达，在有过氧化氢时仍能使其增加，但二者作用并非相加。相反，白藜芦醇阻断了过氧化氢对ET - 1表达的刺激作用。因此，白藜芦醇在生理浓度（0.1微摩尔）时具有显著作用，预计会导致血管舒张，从而有助于降低血压和心血管疾病风险。
Zotero 插件