title: Estrogen receptor beta mediates acute myocardial protection following ischemia.
abstract: BACKGROUND
  Gender differences have been noted in acute ischemia/reperfusion injury. Estrogen and the estrogen receptors (ER) appear to play a critical role in cardiovascular gender differences, given that females have improved myocardial functional recovery associated with decreased tissue inflammation. It has been suggested that ER beta plays a part in decreasing myocardial inflammation following hemorrhage. It remains unknown, however, whether ER beta also may be protective following the more severe insult of complete global, normothermic ischemia/reperfusion injury in the isolated mouse heart.
  
  
  METHODS
  Adult male and female wild-type (WT) and ER beta knockout (ERbKO) mouse hearts were subjected to 20 minutes ischemia and 60 minutes reperfusion (Langendorff model). Myocardial contractile function (+/-dP/dt) was continuously recorded. Heart tissue was analyzed for tumor necrosis factor, interleukin (IL)-1 beta, IL-6, and IL-10 levels as determined by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  Females had markedly improved functional recovery compared with males following ischemia/reperfusion. This recovery was associated with lower levels of myocardial tumor necrosis factor, IL-1 beta, and IL-6 in females. However, ERbKO females exhibited significantly less postischemic functional recovery than WT females and were similar to WT males. Interestingly, increased myocardial production of tumor necrosis factor, IL-1 beta, and IL-6 was noted in ERbKO female hearts in response to ischemia/reperfusion. No significant differences were found between male WT and male ERbKO in postischemic functional recovery and proinflammatory cytokine production.
  
  
  CONCLUSIONS
  ER beta plays a role in the protective effects of estrogen following global, warm ischemia/reperfusion of the isolated mouse heart. This understanding ultimately may enable the development of pharmaceutical agents that harness such protection with minimal collateral sex hormone effects.
authors.affiliation: Department of Surgery, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: Meijing
authors.initials: M
authors.lastname: Wang
authors.forename: Paul R
authors.initials: PR
authors.lastname: Crisostomo
authors.forename: Troy
authors.initials: T
authors.lastname: Markel
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.forename: Keith D
authors.initials: KD
authors.lastname: Lillemoe
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Meldrum
mesh_terms: D000818:Animals; D047629:Estrogen Receptor beta / Q000502:physiology*; D005260:Female; D066298:In Vitro Techniques; D016753:Interleukin-10 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009200:Myocardial Contraction; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism*; D012727:Sex Characteristics; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D047629:Estrogen Receptor beta; D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10