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Updated: Mar 21, 2026

An In Vivo Estrogen Deficiency Mouse Model for Screening Exogenous Estrogen Treatments of Cardiovascular Dysfunction After Menopause
Published on: August 13, 2019
Estrogen and progestogen inhibit NF-κB in atherosclerotic tissues of ovariectomized ApoE (-/-) mice
1a Department of Gynecology and Obstetrics , Beijing Friendship Hospital, Capital Medical University , Beijing , China ;
Objectives:
To determine the effects of estrogen and progestogen treatment on atherosclerotic inflammation and vascular remodeling.
Methods:
Atherosclerosis was induced by feeding ovariectomized ApoE (-/-) mice a cholesterol-rich diet. Estrogen and progestogen were supplied as estradiol valerate (E2V, orally, 0.07 mg/kg/day) and dydrogesterone (DG, orally, 0.2 mg/kg/day), respectively, for 8 weeks. Levels of the vascular inflammatory marker nuclear factor kappa B (NF-κB) and arterial remodeling marker matrix metalloproteinase 9 (MMP-9) were examined. Estrogen receptor (ER) involvement was analyzed by treating with antagonists.
Results:
E2V and DG treatment reduced NF-κB mRNA and protein levels in atherosclerotic tissue from ovariectomized ApoE (-/-) mice, and the difference in expression trended towards statistical significance. Moreover, treatment with the ERβ-specific antagonist significantly increased NF-κB mRNA and protein levels in both the E2V treatment group and the E2V and DG combined treatment group (p < 0.05), suggesting that E2V inhibits NF-κB overexpression in atherosclerotic tissue through ERβ-mediated signaling. However, E2V and DG co-treatment did not significantly affect MMP-9 mRNA or protein expression in atherosclerotic tissue. Introduction of ER antagonists to E2V and DG co-treatment still did not significantly affect MMP-9 expression.
Conclusion:
E2V and DG treatment may inhibit arterial inflammation by regulating ERβ-related signaling pathways.
Insights
Estrogen and progestogen treatment reduced arterial inflammation in mice by impacting nuclear factor kappa B (NF-κB) signaling. This suggests a potential therapeutic role for hormone therapy in managing atherosclerotic inflammation.
Area of Science:
- Cardiovascular Biology
- Endocrinology
- Pharmacology
Background:
- Atherosclerosis involves chronic inflammation and vascular remodeling.
- Hormone replacement therapy (HRT) has complex effects on cardiovascular health.
- Estrogen and progestogen roles in atherosclerosis require further elucidation.
Purpose of the Study:
- To investigate the impact of estradiol valerate (E2V) and dydrogesterone (DG) on atherosclerotic inflammation and vascular remodeling.
- To explore the involvement of estrogen receptors (ERs) in mediating these effects.
Main Methods:
- Ovariectomized ApoE (-/-) mice on a high-cholesterol diet were treated with E2V and DG for 8 weeks.
- Levels of nuclear factor kappa B (NF-κB) and matrix metalloproteinase 9 (MMP-9) were assessed.
- Estrogen receptor antagonist studies were conducted to determine pathway involvement.
Main Results:
- E2V and DG treatment reduced NF-κB mRNA and protein levels in atherosclerotic tissue.
- ERβ antagonism increased NF-κB levels, indicating ERβ-mediated inhibition of NF-κB by E2V.
- MMP-9 expression was not significantly affected by E2V and DG treatment, even with ER antagonist co-administration.
Conclusions:
- E2V and DG treatment may suppress arterial inflammation via ERβ-related signaling pathways.
- The findings suggest a potential mechanism for hormone therapy in managing atherosclerotic inflammation.
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