title: Estrogen and progestogen inhibit NF-κB in atherosclerotic tissues of ovariectomized ApoE (-/-) mice.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  E2V and DG treatment may inhibit arterial inflammation by regulating ERβ-related signaling pathways.
authors.affiliation: a Department of Gynecology and Obstetrics , Beijing Friendship Hospital, Capital Medical University , Beijing , China ;
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.affiliation: b Core Facilities Center , Capital Medical University , Beijing , China ;
authors.forename: H
authors.initials: H
authors.lastname: Zhao
authors.affiliation: c Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College , Beijing , China.
authors.forename: X
authors.initials: X
authors.lastname: Ren
mesh_terms: D000818:Animals; D001057:Apolipoproteins E; D050197:Atherosclerosis / Q000378:metabolism*; D004394:Dydrogesterone / Q000494:pharmacology; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D007249:Inflammation; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D052002:NF-kappa B p50 Subunit / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010052:Ovariectomy; D011372:Progestins / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D011960:Receptors, Estrogen / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D001057:Apolipoproteins E; D004967:Estrogens; D052002:NF-kappa B p50 Subunit; D011372:Progestins; D012333:RNA, Messenger; D011960:Receptors, Estrogen; C073701:Nfkb1 protein, mouse; D004958:Estradiol; D004394:Dydrogesterone; D020780:Matrix Metalloproteinase 9
keywords: Estrogen; MMP-9; NF-κB; atherosclerosis; progestogen