Inhibitory effects of vitamin E on endothelial-dependent adhesive interactions with leukocytes induced by oxidized low density lipoprotein

Leukocyte-endothelial cell interactions, which are mediated by various adhesion molecules, are a crucial event in inflammatory reactions including atherosclerosis. Alpha-tocopherol (alpha-Toc) has been used for protection and therapy of vascular diseases because of its antioxidant activity. The objective of the present study was to determine effect of alpha-Toc on endothelial-dependent adhesive interactions with leukocytes elicited by oxidized low density lipoprotein (oxLDL). Incubation of HUVEC with oxLDL (100 microg/mL) increased expression of proteins and messenger RNA of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) on enzyme immunoassay and northern blotting assay; pretreatment with alpha-Toc reduced in a dose dependent manner. Adherence of polymorphonuclear leukocytes (PMN) or mononuclear leukocytes (MNC) to oxLDL-activated HUVEC was much increased compared with that to unstimulated HUVEC. Treatment of HUVEC with alpha-Toc, monoclonal antibody to ICAM-1 or VCAM-1 inhibited adherence of PMN or MNC in a dose dependent manner. These results suggest that alpha-Toc works as anti-atherogenic agent through inhibiting endothelial-dependent adhesive interactions with leukocytes induced by oxLDL.