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首页> 外文期刊>Chemistry and Physics of Lipids >Determinants of F-2-isoprostane biosynthesis and inhibition in man [Review]
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Determinants of F-2-isoprostane biosynthesis and inhibition in man [Review]

机译：F-2-异前列腺素的生物合成和抑制的决定因素[综述]

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Several cardiovascular risk factors are characterized by the coexistence of low-grade inflammation, enhanced oxidative stress and lipid peroxidation. It has been hypothesized that F-2-isoprostanes, a product of in vivo lipid peroxidation, may transduce the effects of metabolic and hemodynamic abnormalities into increased cardiovascular risk. Thus, the formation of these compounds, including urinary 8-iso-Prostaglandin (PG) F-2alpha, has been investigated in clinical settings putatively associated with oxidant stress. Enhanced lipid peroxidation together with increased in vivo platelet activation have been found in association with the major cardiovascular risk factors. Thus, F-2-isoprostanes may transduce the effects of oxidant stress associated with complex metabolic disorders into specialized forms of cellular activation. In particular, the low-grade inflammatory state characterizing metabolic disorders such as obesity, hypercholesterolemia, type 2 diabetes mellitus, and homozygous homocystinuria may be the primary trigger of thromboxane-dependent platelet activation mediated, at least in part, through enhanced lipid peroxidation. Moreover, oxidative stress may promote endothelial dysfunction through increased production of reactive oxygen species that inactivate nitric oxide. Accumulation and activation of leukocytes plays a key role in atherosclerosis and its complications. Interestingly, neutrophil adhesion induced by minimally modified low-density lipoproteins is mainly mediated by F-2-isoprostanes. Although epidemiological studies suggest an inverse relationship between antioxidant vitamin intake and cardiovascular disease, several clinical trials have obtained conflicting results on the effects of vitamin E supplementation on the risk of cardiovascular events. On the other hand, the use of F-2-isoprostane formation as a biochemical end-point for dose-finding studies of vitamin E supplementation has helped clarifying the unique features of its pharmacodynamic effects on lipid peroxidation. This information could be extremely valuable in the selection of the appropriate patient subgroups that may benefit from antioxidant interventions. (C) 2003 Elsevier Ireland Ltd. All rights reserved. [References: 86]
机译：几种心血管危险因素的特征是低度炎症并存，氧化应激增强和脂质过氧化作用并存。据推测，体内脂质过氧化作用的产物F-2-异前列腺素可能将代谢异常和血液动力学异常的影响转化为心血管风险增加。因此，已经在可能与氧化应激相关的临床环境中研究了包括尿中的8-异前列腺素（PG）F-2α在内的这些化合物的形成。已经发现与主要的心血管危险因素有关的脂质过氧化作用增强以及体内血小板活化的增加。因此，F-2-异前列腺素可能将与复杂代谢紊乱​​相关的氧化应激反应转化为细胞活化的特殊形式。特别是，表征代谢异常（例如肥胖症，高胆固醇血症，2型糖尿病和纯合高半胱氨酸尿症）的低度炎症状态可能是血栓烷依赖性血小板活化（至少部分是通过增强的脂质过氧化作用介导的）的主要触发因素。此外，氧化应激可通过增加使不活跃的一氧化氮失活的活性氧的产生来促进内皮功能障碍。白细胞的积累和活化在动脉粥样硬化及其并发症中起关键作用。有趣的是，最低限度修饰的低密度脂蛋白诱导的嗜中性粒细胞粘附主要是由F-2-异前列腺素介导的。尽管流行病学研究表明抗氧化剂维生素的摄入量与心血管疾病之间呈反比关系，但一些临床试验在补充维生素E对心血管事件风险的影响方面取得了相互矛盾的结果。另一方面，F-2-异前列腺素的形成作为维生素E补充剂剂量研究的生化终点的使用，有助于弄清其对脂质过氧化的药效学作用的独特特征。该信息在选择可能受益于抗氧化剂干预措施的合适患者亚组中可能非常有价值。 （C）2003 Elsevier Ireland Ltd.保留所有权利。 [参考：86]

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