EVIDENCE FOR THE PRESENCE OF OXIDATIVELY MODIFIED LOW-DENSITY LIPOPROTEIN IN ATHEROSCLEROTIC LESIONS OF RABBIT AND MAN
EVIDENCE FOR THE PRESENCE OF OXIDATIVELY MODIFIED LOW-DENSITY LIPOPROTEIN IN ATHEROSCLEROTIC LESIONS OF RABBIT AND MAN
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DOI：
10.1172/jci114271
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发表时间：
1989-10-01
影响因子：
15.9
通讯作者：
STEINBERG, D
中科院分区：
文献类型：
--
作者：
YLAHERTTUALA, S;PALINSKI, W;STEINBERG, D
三条线的证据表明，低密度脂蛋白轻轻地提取人类和兔动脉粥样硬化病变（病变LDL）非常类似的LDL，已在体外氧化修饰。首先，病变LDL表现出氧化LDL的许多物理和化学性质，这些性质不同于血浆LDL：更高的电泳迁移率，更高的密度，更高的游离胆固醇含量，以及磷脂组分中鞘磷脂和溶血磷脂酰胆碱的比例更高。在损伤LDL中发现大量低分子量的载脂蛋白B片段，与体外氧化LDL相似。第二，无论是完整的载脂蛋白B和一些载脂蛋白B片段的病变LDL与抗血清反应的蛋白质印迹，识别丙二醛共轭赖氨酸和4-羟基壬烯醛赖氨酸加合物，这两者都是发现在氧化LDL;血浆LDL和LDL从正常人内膜显示没有这样的反应。第三，病变LDL与氧化LDL具有相同的生物学特性，与血浆LDL相比，病变LDL产生更大的胆固醇酯化刺激，并更快地被巨噬细胞降解。放射性标记的损伤LDL的降解被未标记的损伤LDL、被铜氧化的LDL、被聚肌苷酸和被丙二醛-LDL竞争性抑制，但不被天然LDL抑制，表明被清道夫受体摄取。最后，病变LDL（而不是正常内膜LDL或血浆LDL）是单核细胞的趋化性，是氧化LDL。这些研究提供了强有力的证据表明，动脉粥样硬化病变，无论是在人和兔子，含有氧化修饰的LDL。
Three lines of evidence are presented that low density lipoproteins gently extracted from human and rabbit atherosclerotic lesions (lesion LDL) greatly resembles LDL that has been oxidatively modified in vitro. First, lesion LDL showed many of the physical and chemical properties of oxidized LDL, properties that differ from those of plasma LDL: higher electrophoretic mobility, a higher density, higher free cholesterol content, and a higher proportion of sphingomyelin and lysophosphatidylcholine in the phospholipid fraction. A number of lower molecular weight fragments of apo B were found in lesion LDL, similar to in vitro oxidized LDL. Second, both the intact apo B and some of the apo B fragments of lesion LDL reacted in Western blots with antisera that recognize malondialdehyde-conjugated lysine and 4-hydroxynonenal lysine adducts, both of which are found in oxidized LDL; plasma LDL and LDL from normal human intima showed no such reactivity. Third, lesion LDL shared biological properties with oxidized LDL; compared with plasma LDL, lesion LDL produced much greater stimulation of cholesterol esterification and was degraded more rapidly by macrophages. Degradation of radiolabeled lesion LDL was competitively inhibited by unlabeled lesion LDL, by LDL oxidized with copper, by polyinosinic acid and by malondialdehyde-LDL, but not by native LDL, indicating uptake by the scavenger receptor(s). Finally, lesion LDL (but not normal intimal LDL or plasma LDL) was chemotactic for monocytes, as is oxidized LDL. These studies provide strong evidence that atherosclerotic lesions, both in man and in rabbit, contain oxidatively modified LDL.