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Tocotrienol is the most effective vitamin E for reducing endothelial expression of adhesion molecules and adhesion to monocytes

      Abstract

      α-Tocopherol and its esterified derivatives have been shown to be effective in reducing monocytic-endothelial cell adhesion. However, the effect of α-tocotrienol (α-T3) has not been characterized. In the present study, using human umbilical vein endothelial cells (HUVEC) as the model system, we examined the relative inhibitory effects of α-T3 and other vitamin E derivatives on cell surface adhesion molecule expression under TNF-α stimulation. Using enzyme-linked immunosorbent assay, we demonstrated that α-T3 markedly inhibited the surface expression of vascular cell adhesion molecule-1 in TNF-α activated HUVEC in a dose- and time-dependent manner. The optimal inhibition was observed at 25 μmol/l α-T3 within 24 h (77±5%) without cytotoxicity. In addition, the surface expression of intercellular adhesion molecule-1 and E-selectin were also reduced by 40±7 and 42±5%, respectively. In order to further evaluate the effects of α-T3 on the vascular endothelium, we investigated the ability of monocytes to adhere to endothelial cells. Interestingly, a 63±3% decrease in monocytic cell adherence was observed. Compared to α-tocopherol and α-tocopheryl succinate, α-T3 displayed a more profound inhibitory effect on adhesion molecule expression and monocytic cell adherence. This inhibitory action by α-T3 on TNF-α-induced monocyte adhesion was shown to be NF-κB dependent and was interestingly reversed with co-incubation with farnesol and geranylgeraniol, suggesting a role for prenylated proteins in the regulation of adhesion molecule expression. In summary, the above results suggest that α-T3 is a potent and effective agent in the reduction of cellular adhesion molecule expression and monocytic cell adherence.

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