Tocotrienols and Atherosclerosis

Abstract

The adherence of monocytes to the vascular endothelial cells is an important early event in atherogenesis. Monocyte adherence to endothelial cells is induced by oxidized low density lipoprotein (LDL) and mediated by multiple cell adhesion molecules including vascular cell-adhesion molecule 1 (VCAM-1). Enhanced endothelial expression of these molecules by oxidized LDL has been shown to be a critical step in foam cell formation and the development of atherosclerosis. Recent studies have demonstrated that vitamin E inhibited the expression of mRNA and protein for VCAM-1 by endothelial cells in response to stimulation with oxidized LDL or inflammatory cytokines. Compared to α- tocopherol, α-tocotrienol displayed a more profound inhibitory effect on adhesion molecule expression and monocytic cell adherence. Among the isomers of tocotrienol, δ-tocotrienol was a potent and effective agent for the reduction of cellular VCAM-1 expression and monocytic cell adherence. The inhibitory effects of vitamin E analogs on the adhesiveness of endothelial cells correlated with their intracellular concentrations. Anti-atherogenic effects of tocotrienols may be derived from their properties of cholesterol-lowering effect, protein kinase C inhibition, and modulation of cyclooxygenase cascade. Although recent human studies have raised some doubts on the efficacy of vitamin E in the prevention of progression of atherosclerotic lesions, the experimental studies using tocotrienol strongly support its positive effect on the reduction of risk of atherogenesis. Further studies will be necessary for clarifying the anti-atherogenic effect of tocotrienol and its bioavailability after oral administration.