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 inhibitor of atherosclerosis in animal models. However, the mechanism of its antiatherogenic effect is poorly understood. The aim of our study was to evaluate whether probucol can influence the 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 probucol (50 microM) at different time periods before stimulation with TNFalpha (100 U ml(-1)) or IL-1beta (100 U ml(-1)). The protein expression of VCAM-1 and ICAM-1 was measured by flow cytometry. VCAM-1 mRNA expression was measured by reverse transcription polymerase chain reaction (RT PCR). Probucol time dependently reduced agonist-induced VCAM-1 ( approximately 45%, 48 h) surface protein and mRNA expression ( approximately 40%, 48 h) in HUVEC, but not ICAM-1 surface protein expression. Decreased VCAM-1 expression was associated with reduction ( approximately 40%) of adherence between cytokine-stimulated HUVEC and peripheral blood mononuclear leukocytes (PBMC). Our results suggest that the antiatherogenic effect of probucol may, in part, be due to a downregulation of VCAM-1 expression.

Ibuprofen inhibits adhesiveness of monocytes to endothelium and reduces cellular oxidative stress in smokers and non-smokers.

BACKGROUND: Cigarette smoking is a major risk factor in atherosclerosis and a useful model from which to study chronic inflammation. We compared monocyte function, lipid profiles and inflammatory markers in smokers and non-smokers, before and after oral ibuprofen intake. The adhesion of freshly isolated monocytes to native and tumour necrosis factor alpha (TNFalpha) stimulated human umbilical vein endothelial cells (HUVEC), as well as superoxide anion (O2-) levels and hydrogen peroxide (H2O2) production in resting and phorbol myristate acetate (PMA) stimulated monocytes were determined. MATERIALS AND METHODS: A group of nine smokers without any other coronary risk factor was compared with an age-matched group of 9 non-smokers. Tests were performed before and after a two-week course of oral ibuprofen (600 mg day-1). RESULTS: In smokers before ibuprofen, monocyte adhesion to native and TNFalpha-stimulated HUVEC was increased (P < 0001 and P < 0.01, respectively), and so were O2- levels in native and PMA-stimulated monocytes (P < 0.01 and P < 0.001, respectively). Ibuprofen reduced the adhesion of monocytes to native and stimulated HUVEC (P < 0.001) and O2- generation by resting and PMA-stimulated cells (P < 0.01) in both groups. H2O2 production by resting and PMA-stimulated monocytes was reduced in smokers and non-smokers (P < 0.01). Interestingly, ibuprofen increased HDL cholesterol levels in smokers (P < 0.01) and non-smokers (P < 0.001), and reduced the level of triglycerides in smokers (P < 0.05). CONCLUSION: Oral administration of ibuprofen reduced the adhesion of monocytes to HUVEC, suppressed oxidative stress and increased HDL cholesterol levels in smokers and non-smokers.

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.

[Role of adhesion molecules in interactions of endothelium with leukocytes in inflammatory processes]. / Rola czastek adhezyjnych w interakcjach sródblonka z leukocytami w procesie zapalnym.

This paper reviews recent work regarding the molecules that mediate leukocyte-endothelial cell adhesion, describes the underlying principles of leukocyte migration, and discusses a model of the sequence of events that allows a leukocyte to attach to endothelium and migrate into tissue. Pathophysiological importance of the adhesion molecules in the development of different states of inflammation has been also presented.