Mechanism of cardioprotection following trauma-hemorrhagic shock by a selective estrogen receptor-β agonist: Up-regulation of cardiac heat shock factor-1 and heat shock proteins

Academic Article

Abstract

  • Although 17β-estradiol (E2) administration following trauma-hemorrhage (T-H) improves cardiac function in male rodents, it is not known whether the salutary effects of E2 are mediated via estrogen receptor (ER)-α or ER-β, and whether cardiac heat shock proteins (Hsp) are affected by E2 administration. Male Sprague-Dawley rats underwent T-H (mean BP 40:mmHg for 90:min, then resuscitation). ER-β agonist propyl pyrazole triol (PPT) (5 μg/kg), ER-β agonist diarylpropiolnitrile (DPN) (5 μg/kg), or vehicle (10% DMSO) was injected subcutaneously during resuscitation. At 24:h after T-H or sham operation, cardiac output (CO), stroke volume (SV), mean blood pressure, and ± dP/dtmax were measured (n = 6 rats per group). Cardiac Hsp32, 60, 70, and 90 mRNA/protein expressions and heat shock factor (HSF)-1 DNA binding activity were determined. One-way ANOVA and Tukey's test were used for statistical analysis. CO, SV and ± dP/dtmax decreased significantly after T-H, however, administration of ER-β agonist DPN after T-H restored the above parameters. Moreover, DPN treatment prevented T-H-mediated decrease in Hsp60 mRNA/protein and Hsp90 protein expressions in the heart. Hsp32 and Hsp70 mRNA/protein expression and HSF-1 DNA binding activity in the hearts were increased even above the shams in DPN treated T-H rats. In contrast, no significant change in the above parameters was observed in T-H rats treated with ER-α agonist PPT. Thus, the salutary effects of E2 on cardiac function are mediated via ER-β and ER-β-induced up-regulation of Hsp likely plays a significant role in the E2-mediated cardioprotection after T-H. © 2005 Elsevier Ltd. All rights reserved.
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    Author List

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

  • 185
  • End Page

  • 194
  • Volume

  • 40
  • Issue

  • 1