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.