Raloxifene inhibits cholesterol aortic content but not atherosclerotic plaque size in oophorectomised cholesterol-fed rabbits

Abstract

Raloxifene, a selective oestrogen receptor modulator, is effective in the treatment of osteoporosis without stimulating the breast and the endometrium. Although it is associated with a decrease of cardiovascular risk markers the effect of these changes on atherogenesis, is not clear. In this study, we aimed to investigate the effect of raloxifene on aorta atherogenesis. A total of 32 cholesterol-fed New Zealand white rabbits were studied for 4 months. Twenty-four rabbits underwent bilateral ovariectomy; of these eight received raloxifene (group OR), eight received oestradiol valerate (group OE) and eight received placebo after sterilisation (group OP). Finally, another eight were sham-operated (non-ovariectomised) and received placebo with a hypercholesterolaemic diet (group SP). After the diet, total levels of cholesterol increased in group SP from 111.25 ± 34.8 mg/dl to 1112.25 ± 364.2, in group OP from 122.62 ± 27.7 mg/dl to 1367.37 ± 348.4, in group OE from 65.25 ± 17.01 to 1710.5 ± 356.2 and in group OR from 108.88 ± 15.54 mg/dl to 1407.86 ± 397.7 (no significant differences). At 4 months, in both treated and untreated rabbits, the cholesterol-rich diet caused atherosclerotic lesions affecting 24.51 ± 16.1% for group SP, 30.47 ± 12.2% for group OP, 30.31 ± 18.07% for group OR and 17.91 ± 10.19 for group OE (P < 0.05) of the aortic surface, respectively. Aortic cholesterol expressed as mg of cholesterol/mg aortic weight was found to decrease in raloxifene-treated rabbits: 3.82 ± 2.14 mg col/aortic mg versus 8.55 ± 4.63 (group OP) and 11.97 ± 11.33 (group SP). P < 0.001. Raloxifene reduced aortic cholesterol content but not the atherosclerotic plaque extension in cholesterol-fed ovariectomised rabbits.