Estrogen receptor-α mediates acute myocardial protection in females

Meijing Wang, Paul Crisostomo, George M. Wairiuko, Daniel R. Meldrum

Research output: Contribution to journalArticle

129 Citations (Scopus)

Abstract

Sex differences in myocardial recovery have been reported after acute ischemia and reperfusion injury. Estrogen and the estrogen receptor are critical determinants of cardiovascular sex differences. However, the mechanistic pathways responsible for these differences remain unknown. We hypothesized that estrogen receptor-α is an important modulator of 1) myocardial functional recovery after ischemia and 2) inflammatory signaling via MAPK. To study this, adult male and female wild-type (WT) and estrogen receptor-α knockout (ER1KO) mouse hearts were isolated, perfused via Langendorff model, and subjected to 20 min of ischemia and 60 min of reperfusion. Myocardial contractile function (left ventricular developed pressure and positive and negative first derivative of pressure) was continuously recorded. After ischemia-reperfusion, hearts were assessed for expression of inflammatory cytokines (ELISA) and activation of MAPK and caspase-3 (Western blot analysis). Data were analyzed with two-way ANOVA or Student's t-test, and P < 0.05 was statistically significant. ER1KO females exhibited significantly less functional recovery than WT females and were similar to WT males. Activated ERK was increased in female WT hearts compared with female ER1KO. Activated JNK was decreased in female WT hearts compared with female ER1KO. No significant differences were found between male WT, female WT, male ER1KO, and female ER1KO in activated p38 MAPK, proinflammatory cytokine expression, and proapoptotic signaling. Estrogen receptor-α plays a role in the protection observed in the female heart. Differential activation of MAPK may mediate this protection. Further studies are necessary to delineate these mechanistic pathways.

Original languageEnglish
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume290
Issue number6
DOIs
StatePublished - Jun 2006

Fingerprint

Estrogen Receptors
Ischemia
Sex Characteristics
Reperfusion
Cytokines
p38 Mitogen-Activated Protein Kinases
Ventricular Pressure
Reperfusion Injury
Knockout Mice
Caspase 3
Analysis of Variance
Estrogens
Western Blotting
Enzyme-Linked Immunosorbent Assay
Students
Pressure

Keywords

  • Cardiac ischemia
  • Inflammation
  • Mitogen-activated protein kinase
  • Sex hormones

ASJC Scopus subject areas

  • Physiology

Cite this

Estrogen receptor-α mediates acute myocardial protection in females. / Wang, Meijing; Crisostomo, Paul; Wairiuko, George M.; Meldrum, Daniel R.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 290, No. 6, 06.2006.

Research output: Contribution to journalArticle

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