Raloxifene inhibits cholesterol aortic content but not atherosclerotic plaque size in oophorectomised cholesterol-fed rabbits.
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.
Castelo-Branco
C
C
Menopause Clinic, Department of Gynecology and Obstetrics, Public Health Department, Hospital Clínic Provincial, University of Barcelona, Spain. castelo@medicina.ub.es
Sanjuán
A
A
Casals
Elena
E
Ascaso
C
C
Colodrón
Marta
M
Vicente
J J
JJ
Mercader
Immaculada
I
Escaramís
G
G
Blümel
J E
JE
Ordi
J
J
Vanrell
J A
JA
D000704:Analysis of Variance; D000818:Animals; D001011:Aorta / Q000473:pathology; D019540:Area Under Curve; D001161:Arteriosclerosis / Q000188:drug therapy* / Q000473:pathology*; D001707:Biopsy, Needle; D002791:Cholesterol, Dietary / Q000008:administration & dosage*; D008076:Cholesterol, HDL / Q000032:analysis / Q000097:blood; D008078:Cholesterol, LDL / Q000032:analysis / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D007150:Immunohistochemistry; D008077:Lipoproteins, LDL / Q000032:analysis / Q000187:drug effects; D010052:Ovariectomy; D011336:Probability; D011817:Rabbits; D020849:Raloxifene Hydrochloride / Q000494:pharmacology*; D011897:Random Allocation; D012016:Reference Values; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D012680:Sensitivity and Specificity
D002791:Cholesterol, Dietary; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D008077:Lipoproteins, LDL; D020845:Selective Estrogen Receptor Modulators; D020849:Raloxifene Hydrochloride