Regulation of Vascular Cell Adhesion Molecule-1 and Intercellular Adhesion Molecule-1 in Human Vascular Smooth Muscle Cells

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Abstract

Vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-selectin are inducible proteins involved in cell-cell adhesion. Immunohisto-chemical studies have indicated that human atherosclerotic plaques contain smooth muscle cells (SMCs) that express ICAM-1 and VCAM-1. Recently, we demonstrated that SMCs in culture express a functionally active cytokine-inducible ICAM-1. SMCs and mononuclear cells participate in the local accumulation of cytokines and related growth factors in atherosclerotic lesions. Therefore, we determined the effects of different cytokines and growth factors on mRNA content and cell surface expression of VCAM-1, ICAM-1, and E-selectin in cultured human aortic SMCs by Northern blotting, quantitative polymerase chain reaction amplification, and immunofluorescence flow cytometry. Under basal conditions of cultivation, both VCAM-1 mRNA and membrane expression of VCAM-1 were low and were induced very little by interleukin-1β (100 U/mL). Platelet-derived growth factor or transforming growth factor-β decreased VCAM-1 mRNA basal expression. Treatment of SMCs with tumor necrosis factor-α (TNF-α) led to an increase in both VCAM-1 mRNA and cell surface expression for VCAM-1 in a dose- and time-dependent manner. Interferon-γ induced a weak increase in VCAM-1 mRNA expression, with no synergistic effect on the stimulation by TNF-α. Various differences were noted between the expression of ICAM-1 and VCAM-1 genes, because interleukin-1β induced substantial amounts of ICAM-1 but not VCAM-1. The addition of interferon-γ delays the time at which peak expression of ICAM-1 in response to TNF-α stimulation occurs. Under our conditions, we did not detect any expression of E-selectin by SMCs. These results suggest that cytokines regulate VCAM-1 and ICAM-1 expression on arterial SMCs and could play an important role in the pathophysiology of inflammatory and immune processes in atherosclerosis.

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