Gniwotta C, Morrow J D, Roberts L J, Kühn H
Institute of Biochemistry, University Clinics Charité, Humboldt University, Berlin, F.R. Germany.
Arterioscler Thromb Vasc Biol. 1997 Nov;17(11):3236-41. doi: 10.1161/01.atv.17.11.3236.
Oxidative modification of LDL is believed to play a major role in atherogenesis. As major lipid peroxidation products oxygenated linoleic acid derivatives and oxysterols have been described in human atherosclerotic lesions. Here we report that human lesions contain isoprostanes as peroxidation products of arachidonic acid at a level of 27.1 +/- 21.2 pg/mg wet weight (n = 10), which corresponds to 75.9 +/- 59.3 pg/mg dry weight, n contrast, human umbilical veins (n = 10), which were used as nonatherosclerotic control vessels, contain much smaller amounts of isoprostanes (1.4 +/- 0.7 pg/mg wet weight, which corresponds to 11.7 +/- 6.2 pg/mg dry weight), and there are significant differences between the two types of vessels. As major products of linoleic acid oxidation, racemic hydroxy linoleate isomers were detected in the lesional ester lipids. In human lesions, the hydroxy linoleic acid/linoleic acid ratio was about 0.5%, a result indicating that 5 out of 1000 linoleate residues are present as hydroxylated derivatives. In umbilical veins, no hydroxy linoleic acid could be detected. These data show that human atherosclerotic lesions contain increased amounts of hydroxy linoleic acid isomers and isoprostanes when compared with nonatherosclerotic vessel wall and suggest a link between local lipid peroxidation and progression of atherosclerosis. For evaluation of the degree of lipid peroxidation, the determination of the hydroxy linoleic acid/linoleic acid ratio appears to be more suitable than the isoprostane content.
低密度脂蛋白的氧化修饰被认为在动脉粥样硬化形成中起主要作用。作为主要的脂质过氧化产物,氧化型亚油酸衍生物和氧化甾醇已在人类动脉粥样硬化病变中被描述。在此我们报告,人类病变中含有花生四烯酸过氧化产物异前列腺素,含量为27.1±21.2 pg/mg湿重(n = 10),相当于75.9±59.3 pg/mg干重。相比之下,用作非动脉粥样硬化对照血管的人脐静脉(n = 10)含有少量得多的异前列腺素(1.4±0.7 pg/mg湿重,相当于11.7±6.2 pg/mg干重),两种血管之间存在显著差异。作为亚油酸氧化的主要产物,在病变酯类脂质中检测到了外消旋羟基亚油酸异构体。在人类病变中,羟基亚油酸/亚油酸比率约为0.5%,这一结果表明每1000个亚油酸残基中有5个以羟基化衍生物形式存在。在脐静脉中,未检测到羟基亚油酸。这些数据表明,与非动脉粥样硬化血管壁相比,人类动脉粥样硬化病变中羟基亚油酸异构体和异前列腺素的含量增加,提示局部脂质过氧化与动脉粥样硬化进展之间存在联系。对于评估脂质过氧化程度,测定羟基亚油酸/亚油酸比率似乎比测定异前列腺素含量更合适。