Devaraj S, Li D, Jialal I
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75235-9052, USA.
J Clin Invest. 1996 Aug 1;98(3):756-63. doi: 10.1172/JCI118848.
Low levels of alpha tocopherol are related to a higher incidence of cardiovascular disease and increased intake appears to afford protection against cardiovascular disease. In addition to decreasing LDL oxidation, alpha tocopherol may exert intracellular effects on cells crucial in atherogenesis, such as monocytes. Hence, the aim of this study was to test the effect of alpha tocopherol supplementation on monocyte function relevant to atherogenesis. Monocyte function was assessed in 21 healthy subjects at baseline, after 8 wk of supplementation with d-alpha tocopherol (1,200 IU/d) and after a 6-wk washout phase. The release of reactive oxygen species (superoxide anion, hydrogen peroxide), lipid oxidation, release of the potentially atherogenic cytokine, interleukin 1 beta, and monocyte-endothelial adhesion were studied in the resting state and after activation of the monocytes with lipopolysaccharide at 0, 8, and 14 wk. There was a 2.5-fold increase in plasma lipid-standardized and monocyte alpha tocopherol levels in the supplemented phase. After alpha tocopherol supplementation, there were significant decreases in release of reactive oxygen species, lipid oxidation, IL-1 beta secretion, and monocyte-endothelial cell adhesion, both in resting and activated cells compared with baseline and washout phases. Studies with the protein kinase C inhibitor, Calphostin C, suggest that the inhibition of reactive oxygen species release and lipid oxidation is due to an inhibition of protein kinase C activity by alpha tocopherol. Thus, this study provides novel evidence for an intracellular effect of alpha tocopherol in monocytes that is antiatherogenic.
低水平的α-生育酚与心血管疾病的较高发病率相关，而增加摄入量似乎能预防心血管疾病。除了降低低密度脂蛋白氧化外，α-生育酚可能对动脉粥样硬化形成过程中起关键作用的细胞（如单核细胞）产生细胞内效应。因此，本研究的目的是测试补充α-生育酚对与动脉粥样硬化形成相关的单核细胞功能的影响。在21名健康受试者中，于基线时、补充d-α-生育酚（1200 IU/天）8周后以及6周的洗脱期后评估单核细胞功能。在0、8和14周时，研究了静息状态下以及用脂多糖激活单核细胞后，活性氧（超氧阴离子、过氧化氢）的释放、脂质氧化、潜在致动脉粥样硬化细胞因子白细胞介素1β的释放以及单核细胞与内皮细胞的黏附。在补充阶段，血浆脂质标准化和单核细胞α-生育酚水平增加了2.5倍。与基线期和洗脱期相比，补充α-生育酚后，静息和激活细胞中的活性氧释放、脂质氧化、IL-1β分泌以及单核细胞与内皮细胞的黏附均显著降低。使用蛋白激酶C抑制剂Calphostin C的研究表明，活性氧释放和脂质氧化的抑制是由于α-生育酚对蛋白激酶C活性的抑制。因此，本研究为α-生育酚在单核细胞中的抗动脉粥样硬化细胞内效应提供了新证据。
