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Title: Atherosclerotic lesion development in a novel ovary-intact mouse model of perimenopause.

Authors: Mayer, Loretta P; Dyer, Cheryl A; Eastgard, Rebecca L; Hoyer, Patricia B; Banka, Carole L

Published In Arterioscler Thromb Vasc Biol, (2005 Sep)

Abstract: 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 17beta-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 17beta-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.

PubMed ID: 15994440 Exiting the NIEHS site

MeSH Terms: Animals; Aorta/pathology; Atherosclerosis/pathology*; Atherosclerosis/physiopathology*; Brachiocephalic Trunk/pathology; Carcinogens/pharmacology; Cholesterol, Dietary/blood; Cholesterol, Dietary/pharmacology; Cyclohexanes/pharmacology; Estradiol/pharmacology; Female; Liver/physiology; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Models, Animal; Ovariectomy; Ovary/pathology*; Ovary/physiology*; Perimenopause*; Receptors, LDL/genetics; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.; Vinyl Compounds/pharmacology

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