BAYw6228 suppresses accumulation of macrophages in balloon-induced intimal thickening of rabbit carotid artery

To determine the in vivo activity of BAYw6228 (BAYw), a newly developed 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitor, we examined its effect on balloon catheterization-induced carotid arterial intimal thickening in Japanese white rabbits. In all rabbits weighing approximately 3.5 kg, a balloon catheter was inserted from a peripheral branch of the left external carotid artery to the aorta in order to denude the endothelium of the left common carotid artery. At day 12, they were divided into control and BAYw groups. The latter were subcutaneously injected with BAYw, 1 mg/kg/day, for the following 17 days. At day 15, the second balloon catheterization was performed in the same left common carotid artery in both groups. After another two weeks, the left common carotid artery was removed and stained with Elastica-Masson (EM) and anti-rabbit macrophage antibody (RAM 11). With RAM 11 staining, the number of positive cells in the intimal thickening was markedly decreased in the BAYw group compared with the control group (P<0.01). Compared with the area ratio of the thickened intima/media layer of the control group, that of the BAYw group was significantly decreased to 45% (P<0.05). These results indicate that BAYw prevents accumulation of macrophages and consequently contributes to the inhibition of intimal thickening induced by balloon catheterization.