Low-dose cerivastatin inhibits spontaneous atherogenesis in heterozygous Watanabe hyperlipidemic rabbits

The aim of this study was to investigate whether cerivastatin (BAYw6228), a new potent 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitor, w as able to prevent atherogenesis in heterozygous Watanabe heritable-hyperli pidemic (WHHL) rabbits, a model never tested before using this HMG-CoA redu ctase inhibitor. The heterozygous WHHL rabbits of our breeding developed mi ld hypercholesterolemia along with focal atherosclerotic lesions in the tho racic aorta. A 9-week treatment with cerivastatin at doses comparable to th ose used in humans (50 mu g/kg/day) reduced serum total cholesterol levels (from 94.4 +/- 10.9 to 43.6 +/- 10.5 mg/dl, p < 0.005) and prevented aortic lesion development (intima/media ratio: 0.058 +/- 0.032 vs 0.946 +/- 0.282 in the placebo group, p < 0.0005). Using a panel of monoclonal antibodies specific to macrophages and able to recognize different smooth muscle cell (SMC) phenotypes, we observed that cerivastatin treatment affected the diff erentiation properties of SMCs and drastically reduced SMC and macrophage a ccumulation in the intima of the thoracic aorta. These data show that in th e presence of moderate atherosclerotic lesions, such as those of heterozygo us WHHL rabbits, low doses of cerivastatin exert an antiatherogenic effect. Copyright (C) 2000 S. Karger AG. Basel.