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.
Jialal
I
I
Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9073, USA. jialal.i@pathology.swmed.edu
Devaraj
S
S
Kaul
N
N
D000818:Animals; D001161:Arteriosclerosis / Q000517:prevention & control; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors* / Q000097:blood; D016207:Cytokines / Q000096:biosynthesis; D006801:Humans; D015227:Lipid Peroxidation; D008077:Lipoproteins, LDL / Q000378:metabolism*; D016859:Lipoxygenase Inhibitors; D051379:Mice; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D017382:Reactive Oxygen Species; D014810:Vitamin E / Q000008:administration & dosage / Q000494:pharmacology*
D015815:Cell Adhesion Molecules; D016207:Cytokines; D008077:Lipoproteins, LDL; D016859:Lipoxygenase Inhibitors; D017382:Reactive Oxygen Species; D014810:Vitamin E; D011493:Protein Kinase C