Estrogen and progestogen inhibit NF-κB in atherosclerotic tissues of ovariectomized ApoE (−/−) mice

Abstract

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.