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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:1910.)
© 2005 American Heart Association, Inc.

Atherosclerosis and Lipoproteins

Atherosclerotic Lesion Development in a Novel Ovary-Intact Mouse Model of Perimenopause

Loretta P. Mayer; Cheryl A. Dyer; Rebecca L. Eastgard; Patricia B. Hoyer; Carole L. Banka

From the Department of Biological Sciences (L.P.M., C.A.D.), Northern Arizona University, Flagstaff; La Jolla Institute for Molecular Medicine (R.L.E., C.L.B.), San Diego, Calif; and the Department of Physiology (P.B.H.), University of Arizona, Tucson.

Reprint requests to Loretta P. Mayer, PhD, Northern Arizona University, Department of Biological Sciences, Box 5640, Flagstaff, AZ 86011-5640. E-mail Loretta.Mayer{at}nau.edu

Objective— Since the unexpected results from the Women’s Health Initiative, the possible protective role of estrogen in preventing heart disease in perimenopausal and postmenopausal women is uncertain. This study examined atherosclerotic lesion development in ovariectomized versus follicle-depleted ovary-intact cholesterol-fed female low-density lipoprotein (LDL) receptor–deficient mice.

Methods and Results— We studied lesion development in LDL receptor–deficient mice that were ovariectomized or follicle depleted with 4-vinylcyclohexene diepoxide (VCD) to induce ovarian failure, then treated ± exogenous 17ß-estradiol via pellet implant. At 120 days after start of cholesterol feeding, the extent of lesion in aorta and innominate artery was determined. Lesion area in both locations was similar in vehicle control, VCD-treated, and ovariectomized mice. Replacement with 17ß-estradiol caused lesion reduction (P<0.05) in both arterial locations, but it was most efficacious in suppressing innominate lesion area in VCD-treated mice (12.9±5.2%) compared with ovariectomized mice (40.0±6.04%).

Conclusions— Endocrine status associated with the follicle-depleted ovary influences exogenous estradiol effects during the development of atherosclerotic lesions and, in particular, inhibits lesion progression in the innominate artery.

The goal was to determine whether estrogen treatment altered atherosclerosis development in follicle-deplete ovary-intact mice compared with ovariectomized mice. Ovarian contribution of androgen appeared to augment the protective effects of estrogen, suggesting this new model may provide an improved experimental system to analyze atherosclerosis drugs for perimenopausal and postmenopausal women.

Key Words: atherosclerosis • estrogen supplementation • perimenopause model

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