Probucol Suppresses Macrophage Infiltration and MMP Expression in Atherosclerotic Plaques of WHHL Rabbits

Abstract

Probucol is a lipid-lowering drug that is often prescribed for the treatment of familial hypercholesterolemia. However, it is not known whether probucol can change the lesion quality of atherosclerosis. We examined this possibility using WHHL rabbits, a model of human familial hypercholesterolemia. Three-month-old male WHHL rabbits were treated with either probucol(85 mg/kg/day) or atorvastatin(6 mg/kg/day) for 16 weeks, and their plasma lipid levels and atherosclerotic lesions were compared with those of a control group. We found that probucol treatment reduced the plasma cholesterol levels, but less remarkably than atorvastatin treatment. In spite of this, probucol treatment led to a prominent reduction of aortic en face lesions by 39%(P＜0.01), whereas atorvastatin reduced these by 16%(P＞0.05), compared with those in the control. Histological examinations revealed that the aortic lesions of probucol-treated rabbits were characterized by reduced macrophages and increased smooth muscle cells compared with those from both the control and atorvastatin groups. Furthermore, probucol treatment reduced the coronary artery stenosis and increased the plaque stability. These results suggest that probucol treatment may have beneficial effects on the plaque stability of hypercholesterolemic patients.