PROBUCOL INHIBITS OXIDIZED LOW-DENSITY LIPOPROTEIN-INDUCED ADHESION OF MONOCYTES TO ENDOTHELIAL-CELLS BY REDUCING P-SELECTIN SYNTHESIS IN-VITRO

Probucol (PBC) is an unique antiatherogenic drug producing its effect by antioxidant action rather than hypolipidaemic effect. However, the exact mechanism of its antiatherogenic effect is unclear. Therefore we investigated the PBC effects on the adhesion of monocytes to endothel ial cells, an early event in atherogenesis. Monocyte adhesion to cultu red pig aortic endothelial cells (EC) was induced by oxidized low dens ity lipoprotein (Ox-LDL). To elucidate the mechanisms of the inhibitio n on adhesion, PBC effects on the Ox-LDL-induced expression of P-selec tin, on the synthesis of von Willebrand factor (vWF) and prostacyclin (PGI(2)) were examined. The results showed that Ox-LDL enhanced the ad hesion of monocytes to EC in a concentration-dependent and time-relate d manner. PBC 25, 50 and 75 mu mol/L inhibited the Ox-LDL-induced adhe sion index from 37.3 % to 19.7, 16.6 and 14.6 % respectively (p all < 0.05), and inhibited the Ox-LDL-induced expression of P-selectin from 293.0 ng/ml to 180.0, 132.9 and 132.6 ng/ml respectively. Furthermore, PBC significantly attenuated the Ox-LDL-impaired synthesis of PGI(2) and vWF. These results indicate that PBC may provide a new approach in the prevention of atherosclerosis (AS) by intervention of monocyte ad hesion to EC. In conclusion, PBC inhibits the Ox-LDL-induced adhesion of monocytes to EC. This effect is associated with the inhibition of t he Ox-LDL-induced expression of P-selectin and the protection on the s ynthesis of PGI2.