The expression of adhesion molecules on endothelial cells is inhibited by troglitazone through its antioxidant activity

L Cominacini, U Garbin, A F Pasini, A Davoli, M Campagnola, A Rigoni, L Tosetti, V Lo Cascio
Cell Adhesion and Communication 1999, 7 (3): 223-31
The adhesion of monocytes to endothelium, an early event in atherosclerosis, is mediated by cell adhesion molecules. Signal-transduction pathways for these binding molecules include the translocation of the transcription factor NF-kappaB; moreover, intracellularly generated oxygen-derived free radicals (ODFR) play a major role in this process. This study evaluated the extent to which troglitazone, an oral antidiabetic agent with antioxidant properties, affects the expression of intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin on human umbilical vein endothelial cells (HUVECs), induced by different prooxidant signals such as oxidized LDL and tumor necrosis factor-alpha (TNF-alpha). Furthermore we assessed whether the NF-kappaB activation is modulated by the antioxidative effect of troglitazone. Oxidized LDL not only caused a dose-dependent increase of ICAM-1, VCAM-1 and E-selectin (p<0.001), but also synergically increased their TNF-alpha-induced expression (p<0.001). Troglitazone reduced in a dose-dependent manner the expression of VCAM-1, ICAM-1 and E-selectin induced by different amounts of oxidized LDL (p<0.001). The addition of troglitazone to HUVECs significantly reduced the expression of ICAM-1, VCAM-1 and E-selectin induced by TNF-alpha alone or in combination with oxidized LDL (p<0.001); this reduction was paralleled by a significant fall in NF-kappaB translocation. The results suggest that troglitazone may have prevented NF-kappaB-mediated adhesion molecule expression by exerting its antioxidant effect on ODFR.

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