The effect of alpha-tocopherol on monocyte proatherogenic activity.

Atherosclerosis is the leading cause of morbidity and mortality in Westernized populations. The monocyte is a crucial cell in the genesis of the atherosclerotic lesion and is present during all stages of atherosclerosis. alpha-Tocopherol (AT) is the most active component of the vitamin E family and is the principal and most potent lipid-soluble antioxidant in plasma and LDL. With regard to monocyte function, AT supplementation (1200 IU/d) has been shown to decrease release of reactive oxygen species, lipid oxidation, release of cytokines such as interleukin-1ss (IL-1ss) and tumor necrosis factor-alpha (TNF-alpha) and decrease adhesion of monocytes to human endothelium. The mechanism of inhibition of superoxide and lipid oxidation by monocytes appears to be via inhibition of protein kinase C (PKC), the decrease in IL-1ss and TNF-alpha release by inhibition of 5-lipoxygenase and the inhibition of monocyte-endothelial cell adhesion via decrease in adhesion molecules on monocytes, CD11b and VLA-4 and by decreasing DNA-binding activity of nuclear transcription factor kappaB. Thus, in addition to the decrease in oxidative stress resulting from AT supplementation, as evidenced by decreased F(2)-isoprostanes and LDL oxidizability, AT is anti-inflammatory and exerts beneficial antiatherogenic effects on cells crucial in atherogenesis such as monocytes.