Estrogen receptor beta mediates acute myocardial protection following ischemia

Meijing Wang, Paul R. Crisostomo, Troy Markel, Yue Wang, Keith D. Lillemoe, Daniel R. Meldrum

Research output: Contribution to journalArticle

55 Scopus citations

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)-1β, 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-1β, 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-1β, 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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)233-238
Number of pages6
JournalSurgery
Volume144
Issue number2
DOIs
StatePublished - Aug 1 2008

ASJC Scopus subject areas

  • Surgery

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