Chronic estrogen replacement inhibits aortic intimal hyperplasia independent of serum lipids

The role of estrogens in providing atheroprotection has been well documented in both epidemiologic and experimental studies. This phenomenon has traditionally been attributed to the beneficial lipid-modifying effects of estrogens. Yet lipid alterations may not be the sole mechanism of estrogen-mediated cardiovascular protection. Previous studies have utilized models of either diet- or injury-induced atherosclerosis. As such, the interrelationship between estrogens, lipids, and atherosclerosis remains unclear. The purpose of this study was to determine the effect of ovariectomy with or without estrogen replacement on the development of aortic intimal hyperplasia. Although we acknowledge the influence of estrogens on the lipid profile, we hypothesized that estrogens are atheroprotective independent of changes in serum lipids. Twelve Warhill ewes (7-11 years old) were randomized to sham (2 sheep) operation, ovariectomy (OVx-5 sheep), or ovariectomy with 17 beta-estradiol replacement (OVxE-5 sheep). Serum cholesterol and triglyceride levels were measured at 0, 6, and 12 months. Necropsy was performed at 6 and 12 months with histologic morphometric analysis of the aortoiliac bifurcation. Ovariectomy resulted in intimal thickening in comparison to the sham (p < 0.0001) and hormone replacement group (p < 0.0001). Serum cholesterol and triglyceride levels were similar and normal (40-60 mg/dl) among all groups. Estradiol abrogates aortic intimal hyperplasia following ovariectomy independent of the hormone's effects on lipid metabolism.