Y Chen1, H Zhao2, X Ren3. 1. a Department of Gynecology and Obstetrics , Beijing Friendship Hospital, Capital Medical University , Beijing , China ; 2. b Core Facilities Center , Capital Medical University , Beijing , China ; 3. c Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College , Beijing , China.
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.
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.
Authors: Cassandra D Gipson; Scott Rawls; Michael D Scofield; Benjamin M Siemsen; Emma O Bondy; Erin E Maher Journal: J Neuroinflammation Date: 2021-02-21 Impact factor: 8.322