In human endothelial cells, vitamin E potentiates synthesis of prostacyclin, a potent vasodilator and inhibitor of platelet aggregation (Chan and Leith, 1981; Szczeklik et al., 1985; Thorin et al., 1994; Tran and Chan, 1990).
Vitamin E mediates upregulation of the expression of cytosolic phospholipase A2 and cyclo-oxygenase (Chan et al., 1998a,b; Tran et al., 1996).
Vitamin E enrichment of endothelial cells in culture inhibits the expression of intracellular cell adhesion molecule (ICAM-1) and vascular cell adhesion molecule (VCAM-1) induced by exposure to ox LDL (Cominacini et al., 1997).
Inhibition of Atherogenesis in Animal Models. Studies of antioxidants and atherosclerosis have been conducted using LDL receptor-deficient rabbits, cholesterol-fed rabbits, cholesterol-fed monkeys, cholesterol-fed hamsters, apoE-deficient mice, and LDL receptor-deficient mice (see Steinberg, 1997, for list). It can be concluded that the antioxidant hypothesis of atherosclerosis is strongly supported by a large body of evidence in animal models (Parker et al., 1995; Pratico et al., 1999; Sparrow et al., 1992).
Observational Epidemiological Studies. As shown in Table 6-3, three large prospective cohort studies involving both men and women found an inverse association between estimated dietary intake of vitamin E and coronary heart disease (CHD) risk (Kushi et al., 1996; Rimm et al., 1993; Stampfer et al., 1993). One study (Rimm et al., 1993) included 39,910 male health professionals and found a nonsignificant reduction in CHD risk for both total vitamin E intake and intake of vitamin E from supplements. A second study (Stampfer et al., 1993) included 87,245 female nurses and found the reduction in CHD risk primarily for intake of vitamin E from supplements. In contrast, the third study, which was carried out among 34,486 postmenopausal women (Kushi et al., 1996), found the decrease in risk only for vitamin E intake from foods (not from supplements). Few women in the latter study took high doses of supplemental vitamin E, which may account for the difference in findings from the other two studies. Risk reductions of 30 to 60 percent were found for the highest, relative to the lowest, quintile of intake in these studies.
In a smaller cohort study in Finland (2,748 men, 2,385 women), a statistically significant inverse association between dietary intake of vitamin E and coronary mortality was found in both sexes (Knekt et al., 1994). Although the use of vitamin supplements was