The effect of alpha-tocopherol on monocyte proatherogenic activity

Atherosclerosis is the leading cause of morbidity and mortality in Westerni zed populations. The monocyte is a crucial cell in the genesis of the ather osclerotic lesion and is present during all stages of atherosclerosis. alph a -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 L DL, With regard to monocyte function, AT supplementation (1200 IU/d) has be en shown to decrease release of reactive oxygen species, lipid oxidation, r elease of cytokines such as interleukin-1 beta (IL-1 beta) and tumor necros is factor-alpha (TNF-alpha) and decrease adhesion of monocytes to human end othelium. The mechanism of inhibition of superoxide and lipid oxidation by monocytes appears to be via inhibition of protein kinase C (PKC), the decre ase in IL-1 beta and TNF-alpha release by inhibition of 5-lipoxygenase and the inhibition of monocyte-endothelial cell adhesion via decrease in adhesi on molecules on monocytes, CD11b and VLA-4 and by decreasing DNA-binding ac tivity of nuclear transcription factor kappaB. Thus, in addition to the dec rease in oxidative stress resulting from AT supplementation, as evidenced b y decreased F-2-isoprostanes and LDL oxidizability, AT is anti-inflammatory acid exerts beneficial antiatherogenic effects on cells crucial in atherog enesis such as monocytes.