Reduced progression of atherosclerosis in apolipoprotein E-deficient mice following consumption of red wine, or its polyphenols quercetin or catechin, is associated with reduced susceptibility of LDL to oxidation and aggregation
Reduced progression of atherosclerosis in apolipoprotein E-deficient mice following consumption of red wine, or its polyphenols quercetin or catechin, is associated with reduced susceptibility of LDL to oxidation and aggregation
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DOI：
10.1161/01.atv.17.11.2744
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发表时间：
1997-11-01
影响因子：
8.7
通讯作者：
Aviram, M
中科院分区：
文献类型：
--
作者：
Hayek, T;Fuhrman, B;Aviram, M
在动脉粥样硬化载脂蛋白E基因缺陷(E度)小鼠中，研究了饮用红酒或其主要多酚成分儿茶素或槲皮素对动脉粥样硬化病变的影响，以及与血浆低密度脂蛋白氧化和聚集易感性的关系。取4周龄E级小鼠40只，随机分为4组，每组10只，分别在饮水中添加安慰剂(1.1%酒精)、儿茶素或槲皮素(50 mU/d/只)、红酒(0.5 mg/d/只)，共6周。儿茶素、槲皮素或红酒的摄入对血浆低密度脂蛋白或高密度脂蛋白水平没有影响。与接受安慰剂治疗的E度小鼠相比，接受治疗的小鼠的动脉粥样硬化病变面积分别小39%、46%和48%。根据这些发现，细胞对儿茶素、栎素或红酒的低密度脂蛋白摄取量分别减少了31%、40%和52%。与服用安慰剂组的低密度脂蛋白相比，这些结果与红酒或栎素后分离的低密度脂蛋白的氧化敏感性降低(由铜离子、自由基生成器或巨噬细胞等不同模式诱导)有关，在较小程度上与服用儿茶素后分离的低密度脂蛋白有关。当低密度脂蛋白在体外与红酒或氧化前的多酚预先孵育时，也得到了类似的结果。即使在基础氧化状态(非诱导氧化)，与服用安慰剂的E度小鼠相比，服用儿茶素、栎素或红酒2周的E度小鼠分离出的低密度脂蛋白被发现氧化较少，与服用安慰剂的E度小鼠分离出的低密度脂蛋白相比，低密度脂蛋白相关的过氧化脂质含量分别减少了39%、48%和49%。这种作用可能与多酚处理的小鼠血清对氧磷酶活性增强有关。先前的研究表明，低密度脂蛋白的氧化会导致其聚集。本研究表明，与安慰剂组相比，儿茶素、槲皮素和红酒可使低密度脂蛋白对聚集的敏感性分别降低63%、48%或50%，这一效应在体外也可以表现出来。多酚对低密度脂蛋白氧化的抑制作用可能至少部分与多酚对低密度脂蛋白的直接作用有关，因为槲皮素和儿茶素都被发现通过形成乙醚弯曲键与低密度脂蛋白颗粒结合。因此，我们得出结论，E度小鼠饮食中摄入红酒或其多酚类黄酮、槲皮素以及较少程度的儿茶素可以减缓动脉粥样硬化病变的发展，这一效应与其低密度脂蛋白对氧化和聚集的敏感性降低有关。
The effect of consuming red wine, or its major polyphenol constituents catechin or quercetin, on the development of atherosclerotic lesions, in relation to the susceptibility of plasma LDL to oxidation and to aggregation, was studied in atherosclerotic apolipoprotein E deficient (E degrees) mice. Forty E degrees mice al the age of 4 weeks were divided into four groups, 10 mice in each group, and were supplemented for up to 6 weeks in their drinking water with placebo (1.1% alcohol); catechin or quercetin (50 mu g/d per mouse), or red wine (0.5 mL/d per mouse). Consumption of catechin, quercetin, or red wine had no effect on plasma LDL or HDL cholesterol levels. The atherosclerotic lesion area was smaller in the treated mice by 39%, 46%, and 48%, respectively, in comparison with E degrees mice that were treated with placebo. In accordance with these findings, cellular uptake of LDL derived after catechin, quercetin, or red wine consumption was found to be reduced by 31%, 40%, and 52%, respectively. These results were associated with reduced susceptibility to oxidation (induced by different modes such as copper ions, free radical generator, or macrophages) of LDL isolated after red wine or quercetin and, to a lesser extent after catechin consumption, in comparison with LDL isolated from the placebo group. Similar results were obtained when LDL was preincubated in vitro with red wine or with the polyphenols prior to its oxidation. Even in the basal oxidative state (not induced oxidation), LDL isolated from E degrees mice that consumed catechin, quercetin, or red wine for 2 weeks was found to be less oxidized in comparison with LDL isolated from E degrees mice that received placebo, as evidenced by 39%, 48%, and 49% reduced content of LDL-associated lipid peroxides, respectively. This effect could be related to enhanced serum paraoxonase activity in the polyphenol-treated mice. LDL oxidation was previously shown to lead to its aggregation. The present study demonstrated that the susceptibility of LDL to aggregation was reduced in comparison with placebo-treated mice, by 63%, 48%, or 50% by catechin, quercetin, and red wine consumption, respectively, and this effect could be shown also in vitro. The inhibition of LDL oxidation by polyphenols could be related, at least in part, to a direct effect of the polyphenols on the LDL, since both quercetin and catechin were found to bind to the LDL particle via the formation of an ether bend. We thus conclude that dietary consumption by E degrees mice of red wine or its polyphenolic flavonoids quercetin and, to a lesser extent, catechin leads to attenuation in the development of the atherosclerotic lesion, and this effect is associated with reduced susceptibility of their LDL to oxidation and aggregation.