title: Raloxifene reduces atherosclerosis: studies of optimized raloxifene doses in ovariectomized, cholesterol-fed rabbits.
abstract: OBJECTIVE
  We have previously shown that raloxifene, a selective oestrogen receptor modulator, 35 mg/day inhibits atherosclerosis in ovariectomized, cholesterol-fed rabbits. This effect was only partial as compared to 17beta-oestradiol 4 mg/day; however, plasma raloxifene concentrations were low relative to those obtained in raloxifene-treated women. We therefore investigate the effects of raloxifene at higher doses.
  
  
  METHODS
  The study on atherosclerosis in ovariectomized, cholesterol-fed rabbits (n = 80) compared raloxifene 70 mg/day and 210 mg/day to 17beta-oestradiol 4 mg/day and placebo.
  
  
  RESULTS
  After 48 weeks of therapy, the aortic cholesterol content in the 70 mg/day and 210 mg/day raloxifene treatment groups were 471 +/- 56 nmol/mg protein and 456 +/- 56 nmol/mg protein, respectively. This was significantly less than in the placebo group (654 +/- 69 nmol/mg protein; P < 0.05). In the oestrogen-treated group, the aortic cholesterol content was 357 +/- 62 nmol/mg protein (P < 0.01 as compared to placebo). Differences in serum lipids between the treatment groups could only partly explain the effect on aortic cholesterol content, indicating that additional anti-atherogenic mechanisms may contribute to the decrease in aortic atherosclerosis. This anti-atherosclerotic activity of raloxifene was observed at plasma concentrations comparable to those in postmenopausal women during raloxifene treatment.
  
  
  CONCLUSIONS
  We conclude that clinically relevant raloxifene treatment inhibits aortic atherosclerosis in ovariectomized, cholesterol-fed rabbits.
authors.affiliation: Centre for Clinical and Basic Research, Ballerup Byvej, Ballerup, Denmark.
authors.forename: N H
authors.initials: NH
authors.lastname: Bjarnason
authors.forename: J
authors.initials: J
authors.lastname: Haarbo
authors.forename: I
authors.initials: I
authors.lastname: Byrjalsen
authors.forename: R F
authors.initials: RF
authors.lastname: Kauffman
authors.forename: M P
authors.initials: MP
authors.lastname: Knadler
authors.forename: C
authors.initials: C
authors.lastname: Christiansen
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001011:Aorta / Q000737:chemistry; D001161:Arteriosclerosis / Q000188:drug therapy* / Q000378:metabolism; D002784:Cholesterol / Q000032:analysis; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004958:Estradiol / Q000627:therapeutic use; D005260:Female; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D011817:Rabbits; D020849:Raloxifene Hydrochloride / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use; D020845:Selective Estrogen Receptor Modulators / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use; D014599:Uterus / Q000473:pathology
chemical_list: D002791:Cholesterol, Dietary; D020845:Selective Estrogen Receptor Modulators; D020849:Raloxifene Hydrochloride; D004958:Estradiol; D002784:Cholesterol