Raloxifene and estrogen reduces progression of advanced atherosclerosis - a study in ovariectomized, cholesterol-fed rabbits

The present study investigated the effect of raloxifene, a selective estrogen receptor modulator (SERM), on aortic atherosclerosis in 80 ovariectomized, cholesterol-fed rabbits with pre-induced atherosclerosis. The animals were fed an atherogenic diet containing 240 mg cholesterol/day for 15 weeks, after this period a baseline control group was sacrificed. Thereafter, oral treatment was initiated with either estradiol 4 mg/day (n = 20), raloxifene (210 mg/day) or placebo (n = 20). In the treatment period of 39 weeks, the dietary cholesterol content was reduced to 80 mg cholesterol/day. Postmortem evaluation showed a significantly increased uterine weight induced by estradiol treatment (10.3 +/- 1.2 g), whereas raloxifene intervention caused a decreased uterus weight (1.21 +/- 0.1 g) when compared to placebo (2.48 +/- 0.47 g). Throughout the study, serum lipids increased in all groups to levels seen in very high risk humans. After 58 weeks the cholesterol content in the aorta was 3.18 +/- 0.54 mu mol/cm(2) (38% reduction) in the estradiol group, 3.66 +/- 0.52 mu mol/cm(2) (29% reduction) in the raloxifene group and 5.12 +/- 0.60 mu mol/cm(2) in the placebo group. Analyses of the aortic cholesterol content corrected for time-averaged serum cholesterol revealed that both estradiol and raloxifene therapy significantly reduced the progression of atherosclerosis (P < 0.01 for both) as compared to placebo. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.