The PI3K/Akt pathway mediates the nongenomic cardioprotective effects of estrogen following trauma-hemorrhage

Academic Article


  • OBJECTIVE: To determine whether the nongenomic actions of E2 have any beneficial effect on cardiac function following trauma-hemorrhage and whether those effects are mediated via the PI3K/Akt pathway. SUMMARY BACKGROUND DATA: Since studies suggest that both genomic and nongenomic pathways are involved in mediating the salutary effects of 17β-estradiol (estradiol) following trauma-hemorrhage, we examined if the nongenomic effects of estradiol on cardiac function after trauma-hemorrhage involve the PI3K/Akt pathway. METHODS: Male Sprague-Dawley rats (∼300 g) underwent trauma-hemorrhage (mean blood pressure, 40 mm Hg for 90 min, then resuscitation). Estradiol conjugated to bovine serum albumin (BSA) (estradiol-BSA; 1 mg/kg estradiol) with or without estrogen receptor antagonist (ICI 182,780), PI3K inhibitor (Wortmannin), or vehicle was injected intravenously during resuscitation. At 2 hours after trauma-hemorrhage or sham operation, cardiac output, stroke volume, heart rate, mean arterial pressure, and ±dP/dt were measured. Cardiomyocyte PI3K, p-Akt, Akt protein expressions and apoptosis were also determined. One-way ANOVA and Tukey's test were used for statistical analysis. RESULTS: Cardiac output, stroke volume, and ±dP/dt decreased significantly after trauma-hemorrhage. Administration of estradiol or estradiol-BSA significantly improved these parameters of cardiac function. Although trauma-hemorrhage decreased cardiomyocyte PI3K protein expression and Akt phosphorylation (p-Akt), estradiol or estradiol-BSA treatment following trauma-hemorrhage prevented such decreases in cardiomyocyte PI3K protein expressions and p-Akt. The increase in cardiomyocyte apoptosis was also prevented in rats receiving estradiol-BSA. Co-administration of ICI 182,780 or Wortmannin abolished beneficial effects of estradiol-BSA on cardiac functions following trauma-hemorrhage. CONCLUSION: The PI3K/Akt pathway plays a critical role in mediating the nongenomic salutary effects of estradiol on cardiac function following trauma-hemorrhage. © 2007 Lippincott Williams & Wilkins, Inc.
  • Published In

  • Annals of Surgery  Journal
  • Digital Object Identifier (doi)

    Author List

  • Yu HP; Hsieh YC; Suzuki T; Choudhry MA; Schwacha MG; Bland KI; Chaudry IH
  • Start Page

  • 971
  • End Page

  • 977
  • Volume

  • 245
  • Issue

  • 6