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-Tocopherol on Monocyte Proatherogenic Activity1
2
Departments of
*
Pathology and
Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390-9073
2To whom correspondence should be addressed. E-mail: jialal.i{at}pathology.swmed.edu
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.
-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-
(TNF-
) 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-
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
B. Thus, in addition to the decrease in
oxidative stress resulting from AT supplementation, as evidenced by
decreased F2-isoprostanes and LDL oxidizability, AT is
anti-inflammatory and exerts beneficial antiatherogenic effects on
cells crucial in atherogenesis such as monocytes.
KEY WORDS:
-tocopherol monocytes vitamin E inflammation antioxidant