Selective inhibition by probucol of vascular cell adhesion molecule-1 (VCAM-1) expression in human vascular endothelial cells

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 the recruitment of monocytes in atherosclerosis. Probucol is a potent in hibitor of atherosclerosis in animal models. However, the mechanism of its antiatherogenic effect is poorly understood. The aim of our study was to ev aluate whether probucol can influence the expression of endothelial cell ad hesion molecules and endothelial adhesiveness. The study was performed on c ultured human umbilical vein endothelial cells (HUVEC). HUVEC were pretreat ed with probucol (50 muM) at different time periods before stimulation with TNF alpha (100 U ml(-1)) or IL-1 beta (100 U ml(-1)). The protein expressi on of VCAM-1 and ICAM-1 was measured by flow cytometry. VCAM-1 mRNA express ion was measured by reverse transcription polymerase chain reaction (RT PCR ). Probucol time dependently reduced agonist-induced VCAM-1 (approximate to 45%, 48 h) surface protein and mRNA expression (approximate to 40%, 48 h) in HUVEC, but not ICAM-1 surface protein expression. Decreased VCAM-1 expre ssion was associated with reduction (approximate to 40%) of adherence betwe en cytokine-stimulated HUVEC and peripheral blood mononuclear leukocytes (P BMC). Our results suggest that the antiatherogenic effect of probucol may, in part, be due to a downregulation of VCAM-1 expression. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.