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Updated: Jul 15, 2026
An In Vivo Estrogen Deficiency Mouse Model for Screening Exogenous Estrogen Treatments of Cardiovascular Dysfunction After Menopause
Published on: August 13, 2019
Estrogen increases apoptosis in the arterial wall in a murine atherosclerosis model
Emre Seli1, Ozlem Guzeloglu-Kayisli, Umit A Kayisli
1Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, Connecticut 06520-8063 , USA.
Objective:
To investigate the effect of estrogen (E) on vascular apoptosis during atherosclerotic plaque formation.
Design:
Laboratory study using a murine atherosclerosis model.
Setting:
Academic research center.
Animal(S):
Female mice homozygous for null alleles of LDL receptor (LDL-R(-/-)) in a C57BL/6 background. LDL-R(-/-) mice develop atherosclerosis in a predictable manner when fed a high cholesterol diet.
Intervention(S):
Eight-week-old female LDL-R(-/-) mice (n = 68) were ovariectomized, and implanted subcutaneously with 90-day release pellets containing 0.5 mg of 17beta-estradiol (E(2)) or placebo. Four animals were evaluated at the initiation of the study. Thereafter, four animals from each group were sacrificed weekly for 8 weeks and their aortas studied.
Main Outcome Measure(S):
The effect of E(2) on atherosclerotic plaque development, apoptosis, and cell proliferation was examined in the aorta of ovariectomized LDL-R(-/-) mice that were fed a high cholesterol diet.
Result(S):
Mice treated with E(2) displayed a delay in atherosclerotic plaque formation, associated with an increase in DNA strand breaks in the arterial wall indicative of increased apoptosis, compared to placebo-treated mice. The two groups did not differ in mitotic activity.
Conclusion(S):
In female LDL-R(-/-) mice fed a high cholesterol diet, ovariectomy is associated with increased atherogenesis. The effect of ovariectomy on atherogenesis is reversed by E(2) treatment. In addition to delayed atherogenesis, E(2) treatment of ovariectomized LDL-R(-/-) mice results in an increase in apoptosis in the aortic wall without an effect on the mitotic activity. Our findings suggest that vascular effects of E may be in part mediated by a proapoptotic activity.
