PROBUCOL INHIBITS OXIDATIVE MODIFICATION OF LOW-DENSITY-LIPOPROTEIN
PROBUCOL INHIBITS OXIDATIVE MODIFICATION OF LOW-DENSITY-LIPOPROTEIN
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DOI：
10.1172/jci112349
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发表时间：
1986-02-01
影响因子：
15.9
通讯作者：
STEINBERG, D
中科院分区：
文献类型：
--
作者：
PARTHASARATHY, S;YOUNG, SG;STEINBERG, D
先前的研究已经确定，低密度脂蛋白（LDL）与内皮细胞（EC）孵育后，在结构上发生了广泛的氧化修饰，并且修饰的LDL被巨噬细胞的乙酰基LDL受体特异性识别。因此，原则上，EC修饰的LDL可能有助于动脉粥样硬化形成过程中泡沫细胞的形成。氧化修饰的LDL对EC也有潜在毒性。目前的研究表明，除了普罗布考与EC的LDL孵育过程中防止电泳迁移率的增加，过氧化物的增加，并在随后的易感性增加巨噬细胞降解。它也已被证明，铜离子催化的LDL氧化诱导EC修饰过程中发生的许多相同的变化。加入普罗布考（5 μ M）也阻止了LDL的这种铜催化修饰。最重要的是，从用常规剂量的普罗布考治疗的高胆固醇血症患者的血浆中分离的LDL样品显示出对通过与内皮细胞孵育或在不存在细胞的情况下通过铜离子的氧化修饰具有高度抗性。研究结果表明，假设的，但有趣的可能性，普罗布考，除了其公认的影响血浆低密度脂蛋白水平，可能会抑制动脉粥样硬化通过限制氧化低密度脂蛋白修饰，从而泡沫细胞形成和/或EC损伤。其他具有抗氧化特性的化合物可能表现出类似的行为。
Previous studies have established that low density lipoprotein (LDL) incubated with endothelial cells (EC) undergoes extensive oxidative modification in structure and that the modified LDL is specifically recognized by the acetyl LDL receptor of the macrophage. Thus, in principle, EC-modified LDL could contribute to foam cell formation during atherogenesis. Oxidatively modified LDL is also potentially toxic to EC. The present studies show that addition of probucol during the incubation of LDL with EC prevents the increase in the electrophoretic mobility, the increase in peroxides, and the increase in subsequent susceptibility to macrophage degradation. It has also been shown that oxidation of LDL catalyzed by cupric ion induces many of the same changes occurring during EC modification. Addition of probucol (5 .mu.M) also prevented this copper-catalyzed modification of LDL. Most importantly, samples of LDL isolated from plasma of hypercholesterolemic patients under treatment with conventional dosages of probucol were shown to be highly resistant to oxidative modification either by incubation with endothelial cells or by cupric ion in the absence of cells. The findings suggest the hypothetical but intriguing possibility that probucol, in addition to its recognized effects on plasma LDL levels, may inhibit atherogenesis by limiting oxidative LDL modification and thus foam cell formation and/or EC injury. Other compounds with antioxidant properties might behave similarly.