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

52 Citations (Scopus)

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

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Estrogen Receptor beta
Ischemia
Reperfusion
Interleukin-1
Interleukin-6
Tumor Necrosis Factor-alpha
Reperfusion Injury
Estrogens
Inflammation
Warm Ischemia
Gonadal Steroid Hormones
Knockout Mice
Estrogen Receptors
Interleukin-10
Enzyme-Linked Immunosorbent Assay
Hemorrhage
Cytokines
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Surgery

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Estrogen receptor beta mediates acute myocardial protection following ischemia. / Wang, Meijing; Crisostomo, Paul R.; Markel, Troy; Wang, Yue; Lillemoe, Keith D.; Meldrum, Daniel R.

In: Surgery, Vol. 144, No. 2, 08.2008, p. 233-238.

Research output: Contribution to journalArticle

Wang, M, Crisostomo, PR, Markel, T, Wang, Y, Lillemoe, KD & Meldrum, DR 2008, 'Estrogen receptor beta mediates acute myocardial protection following ischemia', Surgery, vol. 144, no. 2, pp. 233-238. https://doi.org/10.1016/j.surg.2008.03.009
Wang, Meijing ; Crisostomo, Paul R. ; Markel, Troy ; Wang, Yue ; Lillemoe, Keith D. ; Meldrum, Daniel R. / Estrogen receptor beta mediates acute myocardial protection following ischemia. In: Surgery. 2008 ; Vol. 144, No. 2. pp. 233-238.
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