Inhibition of intimal hyperplasia using the selective estrogen receptor modulator raloxifene.
OBJECTIVE
The selective estrogen receptor modulator raloxifene hydrochloride inhibits intimal hyperplasia.


METHODS
Controlled laboratory experiment.


METHODS
Experimental animal model.


METHODS
Forty-three senile female sheep were randomized to sham operation, ovariectomy, or ovariectomy followed by treatment with 17beta-estradiol or raloxifene. Six months after initial operation, we performed necropsy with histological assessment of the aortic bifurcation and bone mineral densitometry and assayed serum lipids.


RESULTS
After 6 months, serum triglyceride and total and high-density lipoprotein cholesterol levels were similar among groups and within the reference range. Ovarian ablation alone resulted in intimal hyperplasia, which was attenuated with estradiol and raloxifene therapy. Furthermore, estradiol and raloxifene therapy reversed ovariectomy-induced decreases in bone mineral density measured using spine morphometry.


CONCLUSIONS
Raloxifene attenuates ovariectomy-induced aortic intimal hyperplasia independent of serum lipid levels. These data suggest that raloxifene, in addition to its beneficial influence on bone density, has direct, beneficial cardiovascular effects.
Selzman
Craig H
CH
Division of Cardiothoracic Surgery, Campus Box C-310, University of Colorado Health Sciences Center, 4200 E Ninth Ave, Denver, CO 80262, USA. craig.selzman@UCHSC.edu
Turner
A Simon
AS
Gaynor
Jaime S
JS
Miller
Stephanie A
SA
Monnet
Eric
E
Harken
Alden H
AH
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000473:pathology; D001161:Arteriosclerosis / Q000517:prevention & control*; D015519:Bone Density / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D004359:Drug Therapy, Combination; D004958:Estradiol / Q000494:pharmacology; D015914:Estrogen Replacement Therapy; D005260:Female; D006965:Hyperplasia / Q000517:prevention & control; D008055:Lipids / Q000097:blood*; D010052:Ovariectomy; D020849:Raloxifene Hydrochloride / Q000494:pharmacology*; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D012756:Sheep; D014280:Triglycerides / Q000097:blood; D017539:Tunica Intima / Q000187:drug effects* / Q000473:pathology*
D008055:Lipids; D020845:Selective Estrogen Receptor Modulators; D014280:Triglycerides; D020849:Raloxifene Hydrochloride; D004958:Estradiol; D002784:Cholesterol