Vitamin E Supplementation Reduces Plasma Vascular Cell Adhesion Molecule-1 and von Willebrand Factor Levels and Increases Nitric Oxide Concentrations in Hypercholesterolemic Patients

Abstract
Up-regulation of vascular cell adhesion molecule-1 (VCAM-1) and reduced nitric oxide (NO) availability represent early characteristics of atherosclerosis. To evaluate whether the antioxidant vitamin E affected the circulating levels of soluble VCAM-1 (sVCAM-1) and the plasma metabolite of NO (nitrite+nitrate) in hypercholesterolemic patients, either vitamin E (either 400 IU or 800 IU/d for 8 wk) or placebo were randomly, double-blindly given to 36 hypercholesterolemic patients and 22 age- and sex-matched controls. At baseline hypercholesterolemic patients showed higher plasma sVCAM-1 (μg⋅liter−1) (591.2 ± 132.5 vs. 505.0 ± 65.6, P < 0.007) and lower NO metabolite (μm) levels (15.9 ± 3.4 vs. 29.2 ± 5.1, P < 0.0001) than controls. In hypercholesterolemic patients, 8 wk vitamin E (but not placebo) treatment significantly decreased circulating sVCAM-1 levels (400 IU: −148.9 ± 84.6, P < 0.009; 800 IU: −204.0 ± 75.7, P < 0.0001; placebo: −4.7 ± 22.6, NS), whereas it increased NO metabolite concentrations (400 IU: +4.0 ± 1.7, P < 0.02; 800 IU: +5.5 ± 0.8, P < 0.0001; placebo: +0.1 ± 1.1, NS) without affecting circulating low- density lipoprotein levels. Changes in both plasma sVCAM-1 and NO metabolite levels showed a trend to significantly correlate (r = −0.515, P = 0.010; and r = 0.435, P = 0.034, respectively) with changes in vitamin E concentrations induced by vitamin E supplementation. In conclusion, isolated hypercholesterolemia both increased circulating sVCAM-1 and reduced NO metabolite concentrations. Vitamin E supplementation counteracts these alterations, thus representing a potential tool for endothelial protection in hypercholesterolemic patients.