title: Increased estrogen receptor alpha in experimental aortic aneurysms in females compared with males.
abstract: BACKGROUND
  Estrogen receptor alpha (ERα) has been identified in the vessel wall, offering vasoprotective effects when upregulated. Estrogens are known to mediate the inflammatory milieu, and inflammation has long been associated with abdominal aortic aneurysm (AAA) formation. Therefore, it is theorized that increased estrogen receptor in females contributes to their relative resistance to AAAs. The objective of this study was to determine gender differences in ERα levels during experimental AAA formation.
  
  
  METHODS
  Infrarenal aortas of male and female C57 mice (n = 18 and n = 16, respectively) were infused with 0.4% elastase. Diameters were measured at days 0 and 14. Aortic messenger RNA expression of ERα was determined on day 3 by reverse transcription-polymerase chain reaction, whereas ERα protein levels were measured via Western blot. Immunohistochemistry using rabbit antibody for ERα was performed on day 14 samples and quantified. Zymography was done for matrix metalloproteinases (MMP)2 and 9 activity levels. Samples of human AAAs were collected and Western blot performed. Data were compared for significance using a student t-test.
  
  
  RESULTS
  Infrarenal aortic diameter increased in elastase-perfused males (ME) by 80% at 14 days after perfusion, whereas females (FE) increased by only 35% (P = 0.0012). FE had ×10 greater ERα messenger RNA expression compared with ME at day 3 (P = 0.003). Similarly, ERα protein levels were 100% higher in FE compared with those in ME on day 14 (P = 0.035). ERα protein levels were 80% higher in female human patients with AAA than those in their male counterparts (P = 0.029). ERα visualized via immunohistochemistry was 1.5 fold higher in FE than ME (P = 0.029). MMP2 and 9 activity levels were decreased in female compared with male aortas.
  
  
  CONCLUSIONS
  This study demonstrates an increase in aortic wall ERα in females compared with males that correlates inversely with MMP activity and AAA formation. These findings, coupled with observations that exogenous estrogen inhibits AAA formation in males, further suggest that estrogen supplementation may be important to prevent AAA formation and growth.
authors.affiliation: Division of Vascular Surgery, University of Michigan, Ann Arbor, MI.
authors.forename: Adriana
authors.initials: A
authors.lastname: Laser
authors.forename: Abhijit
authors.initials: A
authors.lastname: Ghosh
authors.forename: Karen
authors.initials: K
authors.lastname: Roelofs
authors.forename: Omar
authors.initials: O
authors.lastname: Sadiq
authors.forename: Brendan
authors.initials: B
authors.lastname: McEvoy
authors.forename: Paul
authors.initials: P
authors.lastname: DiMusto
authors.forename: Jon
authors.initials: J
authors.lastname: Eliason
authors.forename: Gilbert R
authors.initials: GR
authors.lastname: Upchurch
mesh_terms: D000818:Animals; D017544:Aortic Aneurysm, Abdominal / Q000209:etiology / Q000378:metabolism*; D004958:Estradiol / Q000502:physiology; D047628:Estrogen Receptor alpha / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000032:analysis; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D012727:Sex Characteristics
chemical_list: D047628:Estrogen Receptor alpha; D004958:Estradiol; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
keywords: Aortic aneurysm; Estrogen; Gender difference