Pii: S0021-9150(00)00470-6

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 (10.391.2 g), whereas raloxifene intervention caused a decreased uterus weight (1.2190.1 g) when compared to placebo (2.4890.47 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 3.1890.54 mmol/cm (38% reduction) in the estradiol group, 3.6690.52 mmol/cm (29% reduction) in the raloxifene group and 5.1290.60 mmol/cm 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 (PB0.01 for both) as compared to placebo. © 2001 Elsevier Science Ireland Ltd. All rights reserved.