Inhibition of THP-1 cell adhesion to endothelial cells by α-tocopherol and α-tocotrienol is dependent on intracellular concentration of the antioxidants

Vitamin E analogs such as α-tocopherol and α-tocotrienol have been shown to reduce endothelial expression of adhesion molecules. The reactivity of α-tocopherol and α-tocotrienol in inhibiting lipid peroxidation in vitro was essentially identical but the inhibition of adhesion of THP-1 cells, a monocytic-“like” cell line, to endothelial cells differs substantially. To determine the mechanism underlying this response, human umbilical vein endothelial cells (HUVECs) were assessed for their ability to accumulate vitamin E analogs. α-Tocotrienol accumulated in HUVECs to levels approximately 10-fold greater than that of α-tocopherol. The decrease in expression of vascular cell adhesion molecule-1 (VCAM-1) and the adhesion of THP-1 cells to HUVECs by α-tocopherol and α-tocotrienol was also determined. Both α-tocopherol and α-tocotrienol suppressed VCAM-1 expression and adhesion of THP-1 cells to HUVECs in a concentration-dependent manner. The efficacy of tocotrienol for reduction of VCAM-1 expression and adhesion of THP-1 cells to HUVECs was also 10-fold higher than that of tocopherol. The inhibitory effects of vitamin E analogs on the adhesiveness of endothelial cells clearly correlated with their intracellular concentrations. The data demonstrated that, in assessing the biological responses of antioxidants, intracellular accumulation and metabolism were additional important factors that must be considered.