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 endothelial cells, an early event in atherogenesis. Monocyte adhesion to cultured pig aortic endothelial cells (EC) was induced by oxidized low density lipoprotein (Ox-LDL). To elucidate the mechanisms of the inhibition on adhesion, PBC effects on the Ox-LDL-induced expression of P-selectin, on the synthesis of von Willebrand factor (vWF) and prostacyclin (PGI2) were examined. The results showed that Ox-LDL enhanced the adhesion of monocytes to EC in a concentration-dependent and time-related manner. PBC 25, 50 and 75 micromol/L inhibited the Ox-LDL-induced adhesion 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 PGI2 and vWF. These results indicate that PBC may provide a new approach in the prevention of atherosclerosis (AS) by intervention of monocyte adhesion to EC. In conclusion, PBC inhibits the Ox-LDL-induced adhesion of monocytes to EC. This effect is associated with the inhibition of the Ox-LDL-induced expression of P-selectin and the protection on the synthesis of PGI2.
Li
L X
LX
Department of Cardiopulmonary Pharmacology, Hengyang Medical College, Hunan, PR China.
Chen
J X
JX
Liao
D F
DF
Yu
L
L
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002450:Cell Communication / Q000187:drug effects; D002478:Cells, Cultured; D004336:Drug Antagonism; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D006801:Humans; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D009000:Monocytes / Q000166:cytology / Q000502:physiology*; D019007:P-Selectin / Q000502:physiology*; D011341:Probucol / Q000494:pharmacology*; D013552:Swine
D000924:Anticholesteremic Agents; D008077:Lipoproteins, LDL; D019007:P-Selectin; C099252:oxidized low density lipoprotein; D011341:Probucol