LIPOPROTEIN(A) ENHANCES THE EXPRESSION OF INTERCELLULAR-ADHESION MOLECULE-1 IN CULTURED HUMAN UMBILICAL VEIN ENDOTHELIAL-CELLS

Background-We reported an increase in serum lipoprotein(a) [Lp(a)] lev els in patients with thromboangiitis obliterans, suggesting that Lp(a) could also contribute to the pathogenesis of cardiovascular diseases by a mechanism different from atherosclerosis. Adhesion molecules were shown to contribute to the development of not only atherosclerotic bu t also inflammatory vascular diseases, Methods and Results-We evaluate d the effect of Lp(a) on the expression of intercellular adhesion mole cule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, and E-selecti n in human umbilical vein endothelial cells by a cell ELISA. Lp(a) dra matically enhanced the levels of ICAM-1 in a dose-dependent manner. A discernible increase ill ICAM-1 expression was observed at a physiolog ical concentration of 0.26 mmol cholesterol/L Lp(a) after 48-hour incu bation. A 1.8-fold increase in ICAM-1 expression was observed 46 hours after the addition of Lp(a) (1.04 mmol cholesterol/L), Northern blot analysis demonstrated that the amount of ICAM-1 mRNA was increased aft er treatment with Lp(a), III contrast to ICAM-1, the expression of VCA M-1 and E-selectin was not significantly affected by Lp(a). Lp(a-) [ap olipoprotein(a)-removed Lp(a) by reduction with dithiothreitol] and LD L had no significant effect on the expression of ICAM-1, In contrast, recombinant apolipoprotein(a) protein alone significantly enhanced ICA M-1 expression, Lp(a) decreased the level of active transforming growt h factor (TGF)-beta in the conditioned medium. Furthermore, recombinan t TGF-beta significantly decreased the Lp(a)-induced ICAM-1 expression , These findings suggested that Lp(a) may enhance the ICAM-1 expressio n by decreasing active TGF-beta level. Conclusions-Lp(a) could contrib ute to the development of cardiovascular diseases by enhancing the exp ression of ICAM-1 in endothelial cells.