Selective inhibition by alpha-tocopherol of vascular cell adhesion molecule-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 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.
Regional Center for Atherosclerosis Research, Pomeranian Academy of Medicine, Szczecin, 70-111, Poland.
D
D
Zapolska-Downar
A
A
Zapolski-Downar
M
M
Markiewski
A
A
Ciechanowicz
M
M
Kaczmarczyk
M
M
Naruszewicz
D001161:Arteriosclerosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion; D002460:Cell Line; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D009000:Monocytes / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis*; D014810:Vitamin E / Q000494:pharmacology*
D012333:RNA, Messenger; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D014810:Vitamin E