Lx. Li et al., PROBUCOL INHIBITS OXIDIZED LOW-DENSITY LIPOPROTEIN-INDUCED ADHESION OF MONOCYTES TO ENDOTHELIAL-CELLS BY REDUCING P-SELECTIN SYNTHESIS IN-VITRO, Endothelium (Print), 6(1), 1998, pp. 1-8
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.