Inhibition of Intimal Hyperplasia Using the Selective Estrogen Receptor Modulator Raloxifene

HYPOTHESIS: The selective estrogen receptor modulator raloxifene hydrochloride inhibits intimal hyperplasia. DESIGN: Controlled laboratory experiment. SETTING: Experimental animal model. INTERVENTION AND MAIN OUTCOME MEASURES: 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.