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Polyphenols bind to low density lipoprotein at biologically relevant concentrations that are protective for heart disease
Archives of Biochemistry and Biophysics ( IF 3.8 ) Pub Date : 2020-09-30 , DOI: 10.1016/j.abb.2020.108589
Wei-Cheng Tung , Bryan Rizzo , Yusef Dabbagh , Suraj Saraswat , Mark Romanczyk , Edelsys Codorniu-Hernández , Rocio Rebollido-Rios , Paul W. Needs , Paul A. Kroon , Njara Rakotomanomana , Olivier Dangles , Karen Weikel , Joe Vinson

There is ample evidence in the epidemiological literature that polyphenols, the major non-vitamin antioxidants in plant foods and beverages, have a beneficial effect on heart disease. Until recently other mechanisms which polyphenols exhibit such as cell signaling and regulating nitric oxide bioavailability have been investigated. The oxidation theory of atherosclerosis implicates LDL oxidation as the beginning step in this process. Nine polyphenols from eight different classes and several of their O-methylether, O-glucuronide and O-sulfate metabolites have been shown in this study to bind to the lipoproteins and protect them from oxidation at lysosomal/inflammatory pH (5.2), and physiological pH (7.4). Polyphenols bind to the apoprotein at pH 7.4 with Kb > 106 M−1 and the number of molecules of polyphenols bound per LDL particle under saturation conditions varied from 0.4 for ferulic acid to 13.1 for quercetin. Competition studies between serum albumin and LDL show that substantial lipoprotein binding occurs even in the presence of a great molar excess of albumin, the major blood protein. These in vitro results are borne out by published human supplementation studies showing that polyphenol metabolites from red wine, olive oil and coffee are found in LDL even after an overnight fast. A single human supplementation with various fruit juices, coffee and tea also produced an ex vivo protection against lipoprotein oxidation under postprandial conditions. This in vivo binding is heart-protective based on published olive oil consumption studies. Relevant to heart disease, we hypothesize that the binding of polyphenols and metabolites to LDL functions as a transport mechanism to carry these antioxidants to the arterial intima, and into endothelial cells and macrophages. Extracellular and intracellular polyphenols and their metabolites are heart-protective by many mechanisms and can also function as potent “intraparticle” and intracellular antioxidants due to their localized concentrations that can reach as high as the micromolar level. Low plasma concentrations make polyphenols and their metabolites poor plasma antioxidants but their concentration in particles such as lipoproteins and cells is high enough for polyphenols to provide cardiovascular protection by direct antioxidant effects and by other mechanisms such as cell signaling.



中文翻译:

多酚以生物学相关浓度结合低密度脂蛋白,可保护心脏病

流行病学文献中有充分的证据表明,多酚是植物性食品和饮料中的主要非维生素抗氧化剂,对心脏病具有有益的作用。直到最近,还研究了多酚表现出的其他机制,例如细胞信号传导和调节一氧化氮的生物利用度。动脉粥样硬化的氧化理论暗示LDL氧化是该过程的开始步骤。在这项研究中显示,来自八种不同类别的九种多酚及其几种O-甲基醚,O-葡萄糖醛酸和O-硫酸盐代谢物与脂蛋白结合,并在溶酶体/炎性pH(5.2)和生理pH下保护其免受氧化(7.4)。多酚在pH 7.4时与脱辅基蛋白结合,K b  > 10 6  M-1和饱和条件下每个LDL粒子结合的多酚分子数从阿魏酸的0.4到槲皮素的13.1不等。血清白蛋白与LDL之间的竞争研究表明,即使存在大量摩尔过量的主要血液蛋白白蛋白,也会发生大量脂蛋白结合。这些体外研究结果已由已发表的人体补充研究证实,表明即使在通宵禁食后,低密度脂蛋白中也发现了来自红酒,橄榄油和咖啡的多酚代谢产物。单一人体补充各种果汁,咖啡和茶也可在餐后条件下提供针对脂蛋白氧化的离体保护。这种体内根据已发表的食用橄榄油的研究,这种结合具有心脏保护作用。与心脏病有关,我们假设多酚和代谢物与LDL的结合是一种将这些抗氧化剂运送到动脉内膜以及进入内皮细胞和巨噬细胞的转运机制。细胞外和细胞内多酚及其代谢物通过许多机制对心脏具有保护作用,并且由于它们的局部浓度可高达微摩尔水平,因此还可以用作有效的“颗粒内”和细胞内抗氧化剂。

更新日期:2020-09-30
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