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 important 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 formation after balloon injury in normocholesterolemic rabbits and examined whether probucol could inhibit the proliferation of rabbit cultured VSMC stimulated by fetal bovine serum (FBS). Probucol. inhibited the formation of neointima by about 63% 2 weeks after balloon injury. Probucol inhibited the increase in the number of cultured VSMCs and bromodeoxyuridine (BrdU) incorporation stimulated by 10% FBS in a dose-dependent manner. Also, 10% FBS stimulated the activities of mitogen-activated protein kinase (MAP kinase) and protein kinase C (PKC) in cultured VSMCs. 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.