PROBUCOL INHIBITS NEOINTIMAL FORMATION IN CAROTID ARTERIES OF NORMOCHOLESTEROLEMIC RABBITS AND THE PROLIFERATION OF CULTURED RABBIT VASCULAR SMOOTH-MUSCLE CELLS

The proliferation of vascular smooth muscle cells (VSMCs) plays an imp ortant role in the formation of atherosclerotic lesions and restenosis after angioplasty. It has been suggested that probucol inhibits VSMCs proliferation, but this effect has not been directly demonstrated. In this study we investigated the effect of probucol on neointimal forma tion after balloon injury in normocholesterolemic rabbits and examined whether probucol could inhibit the proliferation of rabbit cultured V SMC stimulated by fetal bovine serum (FBS). Probucol. inhibited the fo rmation of neointima by about 63% 2 weeks after balloon injury. Probuc ol inhibited the increase in the number of cultured VSMCs and bromodeo xyuridine (BrdU) incorporation stimulated by 10% FBS in a dose-depende nt manner. Also, 10% FBS stimulated the activities of mitogen-activate d protein kinase (MAP kinase) and protein kinase C (PKC) in cultured V SMCs. Probucol inhibited these activities in a dose-dependent fashion. These results suggest that probucol may inhibit neointimal formation after balloon injury in normocholesterolemic rabbits by preventing the proliferation of VSMCs via inactivation of MAP kinase and PKC.