A role of PPAR-γ in androstenediol-mediated salutary effects on cardiac function following trauma-hemorrhage

Academic Article


  • OBJECTIVE: To examine the mechanism by which androstenediol improves cardiac function following trauma-hemorrhage (T-H). SUMMARY BACKGROUND DATA: Androstenediol administration improves cardiovascular function and attenuates proinflammatory cytokine production following T-H. Activation of the peroxisome proliferator-activated receptor-gamma (PPAR-γ) has been shown to be protective following ischemic conditions. We hypothesized that PPAR-γ activation plays a role in the androstenediol-mediated salutary effects on cardiac function following T-H. METHODS: Male rats underwent laparotomy and hemorrhagic shock (40 mm Hg for 90 minutes), followed by resuscitation with 4 times the shed blood volume in the form of Ringer's lactate. Androstenediol (1 mg/kg body weight, i.v.) was administrated at the end of resuscitation. In a separate group of animals, a PPAR-γ antagonist (GW9662) was administered simultaneously with androstenediol and animals were killed at 5 hours thereafter. RESULTS: A decrease in cardiac function and an increase in IL-6 and iNOS gene expression were observed following T-H. Androstenediol treatment normalized cardiac function, increased PPAR-γ DNA binding activity, attenuated IL-6 and iNOS gene expressions, and reduced plasma IL-6. Plasma 15-deoxy-Δ12, 14-prostaglandin J2 (PGJ2, an endogenous PPAR-γ agonist) levels were also increased in androstenediol-treated T-H rats, but these levels were lower than those observed in shams. Coadministration of PPAR-γ antagonist along with androstenediol, however, prevented the androstenediol-mediated reduction in cardiac iNOS and IL-6 expressions and abolished the improvements in cardiac function. CONCLUSION: The androstenediol-mediated salutary effects on cardiac function following T-H appear to be mediated at least in part via PPAR-γ activation, which down-regulates IL-6 and iNOS gene expression in the heart. Copyright © 2006 by Lippincott Williams & Wilkins.
  • Published In

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

    Author List

  • Shimizu T; Szalay L; Hsieh YC; Suzuki T; Choudhry MA; Bland KI; Chaudry IH
  • Start Page

  • 131
  • End Page

  • 138
  • Volume

  • 244
  • Issue

  • 1