Selective inhibition by alpha-tocopherol of vascular cell adhesion molecule-1 expression in human vascular...

An early event in atherogenesis is the adhesion of monocytes to endothelium via adhesion molecules such as VCAM-1 and intracellular adhesion molecule-1 (ICAM-1). It has been suggested that VCAM-1 plays a very important role in recruitment of monocytes in atherosclerosis. Several studies suggest that vitamin E has antiatherosclerotic properties. However, the mechanism of its antiatherogenic effect awaits elucidation. The aim of our study was to evaluate whether alpha-tocopherol can influence expression of endothelial cell adhesion molecules and endothelial adhesiveness. The study was performed on cultured human umbilical vein endothelial cells (HUVEC). HUVEC were pretreated with alpha-tocopherol (50 micromol/l) in different times before stimulation with TNFalpha (100 U/ml) or IL-1beta (100 U/ml). Protein expression of VCAM-1 and ICAM-1 was measured by flow cytometry. mRNA expression of VCAM-1 was measured by reverse transcription polymerase chain reaction (RT-PCR). alpha-Tocopherol time dependently reduced agonist-induced VCAM-1 in both surface protein (about 40%, 48 h) and mRNA (about 35%, 48 h) expression in HUVEC but not ICAM-1 surface protein expression. Inhibitory effect of alpha-tocopherol was dependent on culture condition of HUVEC. Decreased VCAM-1 expression was associated with reduction (about 40%) of adherence between cytokine-stimulated HUVEC and peripheral blood mononuclear leukocytes (PBMC). Our results suggest that the antiatherogenic effect of alpha-tocopherol may in part be due to a downregulation of VCAM-1 expression.