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


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.
Mayer
Loretta P
LP
Department of Biological Sciences, Northern Arizona University, Box 5640, Flagstaff, AZ 86011-5640, USA. Loretta.Mayer@nau.edu
Dyer
Cheryl A
CA
Eastgard
Rebecca L
RL
Hoyer
Patricia B
PB
Banka
Carole L
CL
D000818:Animals; D001011:Aorta / Q000473:pathology; D050197:Atherosclerosis / Q000473:pathology* / Q000503:physiopathology*; D016122:Brachiocephalic Trunk / Q000473:pathology; D002273:Carcinogens / Q000494:pharmacology; D002791:Cholesterol, Dietary / Q000097:blood / Q000494:pharmacology; D003510:Cyclohexanes / Q000494:pharmacology; D053138:Cyclohexenes; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D008099:Liver / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D023421:Models, Animal; D010052:Ovariectomy; D010053:Ovary / Q000473:pathology* / Q000502:physiology*; D047648:Perimenopause; D011973:Receptors, LDL / Q000235:genetics; D014753:Vinyl Compounds / Q000494:pharmacology
D002273:Carcinogens; D002791:Cholesterol, Dietary; D003510:Cyclohexanes; D053138:Cyclohexenes; D011973:Receptors, LDL; D014753:Vinyl Compounds; D004958:Estradiol; C012606:4-vinyl-1-cyclohexene dioxide