Cachia O, Léger C L, Descomps B
Laboratoire de Biologie et Biochimie des Lipides, EA 2033, Institut de Biologie, Faculté de Médecine, Université de Montpellier, France.
Atherosclerosis. 1998 Jun;138(2):263-9. doi: 10.1016/s0021-9150(98)00028-8.
Vitamin E (alpha-tocopherol) is a potent peroxyl radical scavenger. According to the oxidative theory of atherosclerosis, it prevents oxidation of low-density lipoprotein (LDL) and thereby lowers the risk of cardiovascular disease. It also mediates cell actions, and specifically decreases monocyte superoxide anion-production (O2.--production), which is involved in LDL oxidation. We investigated whether alpha-tocopherol-containing LDL decreases this production in a manner dependent on the LDL alpha-tocopherol content (the alpha-tocopherol/apoB molar ratio) in human, phorbol ester-stimulated, adherent monocytes. We found that O2.--production was inhibited by native LDL (n-LDL) in a manner highly sensitive to the increasing alpha-tocopherol content (range 4.5 8). In addition: (1) inhibition was greater when alpha-tocopherol was associated to acetylated LDL (ac-LDL), the maximal percentage of inhibition being 80% as opposed to 35% for n-LDL; (2) the alpha-tocopherol overloading of either form of LDL did not produce further inhibition; (3) the free form of alpha-tocopherol produced lower inhibition compared with the lipoprotein-associated forms; (4) inhibition was not related to the cell content of alpha-tocopherol. We propose that the cell targeting of alpha-tocopherol is crucial to the inhibition of monocyte O2.--production, and thus that the role of normal LDL-alpha-tocopherol contents (range 6-8) in the prevention of atherogenic processes needs to be reexamined.
维生素E（α-生育酚）是一种有效的过氧自由基清除剂。根据动脉粥样硬化的氧化理论，它可防止低密度脂蛋白（LDL）氧化，从而降低心血管疾病风险。它还介导细胞作用，特别是减少单核细胞超氧阴离子生成（O₂⁻生成），而单核细胞超氧阴离子生成与LDL氧化有关。我们研究了含α-生育酚的LDL是否以依赖于LDL中α-生育酚含量（α-生育酚/载脂蛋白B摩尔比）的方式降低人佛波酯刺激的贴壁单核细胞中的这种生成。我们发现，天然LDL（n-LDL）以对α-生育酚含量增加高度敏感的方式（范围4.5 - 8）抑制O₂⁻生成。此外：（1）当α-生育酚与乙酰化LDL（ac-LDL）结合时抑制作用更强，最大抑制百分比为80%，而n-LDL为35%；（2）两种形式的LDL中α-生育酚超载均未产生进一步抑制；（3）游离形式的α-生育酚与脂蛋白结合形式相比产生的抑制作用更低；（4）抑制作用与细胞中的α-生育酚含量无关。我们提出，α-生育酚的细胞靶向作用对于抑制单核细胞O₂⁻生成至关重要，因此正常LDL-α-生育酚含量（范围6 - 8）在预防动脉粥样硬化过程中的作用需要重新审视。
