Tocopherol

Low levels of «-tocopherol are related to a higher incidence of cardiovascular disease, and an increased intake of the vitamin appears to afford protection against cardiovascular disease (Devaraj et al., 1996). In addition to decreasing LDL oxidation, «-tocopherol has been suggested to exert intracellular effects on the adhesive properties of cells (e.g., monocytes and platelets) that are crucial in atherogenesis (Devaraj and Jialal, 1998; Devaraj et al., 1996). Pretreatment of HUVEC with «-tocopherol has been shown to downregulate agonist (interleukin-1, thrombin, or PMA)-induced monocytic adhesion to HUVEC (Faruqi et al., 1994). Such inhibition correlated with

LA (mM, 48 hpre) - - 0.05 0.1 0.25 0.5 PMA (100 nM, 24h) - + + + + +

Figure 9 Dose relationship of a-lipoate pretreatment on PMA-induced ICAM-1 expression in human vascular endothelial (ECV) cells. ECV cells were pretreated with a-lipoate (0500 ¡jlM, LA) for 48 hr and then activated with 100 nM PMA for 24 hr. Expression of ICAM-1 on ECV cells was determined using flow cytometry. Data are means ± SD of at least three experiments. *p < 0.01 when compared with PMA-induced ICAM-1 expression (Roy et al, 1998).

LA (mM, 48 hpre) - - 0.05 0.1 0.25 0.5 PMA (100 nM, 24h) - + + + + +

Figure 9 Dose relationship of a-lipoate pretreatment on PMA-induced ICAM-1 expression in human vascular endothelial (ECV) cells. ECV cells were pretreated with a-lipoate (0500 ¡jlM, LA) for 48 hr and then activated with 100 nM PMA for 24 hr. Expression of ICAM-1 on ECV cells was determined using flow cytometry. Data are means ± SD of at least three experiments. *p < 0.01 when compared with PMA-induced ICAM-1 expression (Roy et al, 1998).

a decrease in steady-state levels of E-selectin mRNA and cell surface expression of E-selectin (Faruqi etal., 1994). Probucol also showed a similar effect as that of «-tocopherol on cell adhesion (Faruqi et al., 1994). Cotreatment of lipoate and a-tocopherol has been observed to be more effective in down-regulating the agonist-induced adhesion of leukocytes to endothelial cells compared to the treatment of endothelial cells with either of the antioxidants alone (Roy et al., 1998). Cytokine-stimulated cell surface expression of VCAM-1 and E-selectin, but not of ICAM-1, has been reported to be inhibited by a-tocopherol succinate (Erl et al., 1997). However, such effects were not exerted either by a-tocopherol or its acetate derivative (Erl et al., 1997).

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