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Cardioprotective effects of peroxisome proliferator activated receptor γ activators on acute myocarditis: anti-inflammatory actions associated with nuclear factor κB blockade
  1. Z Yuan1,*,
  2. Y Liu1,
  3. Y Liu1,
  4. J Zhang1,
  5. C Kishimoto2,
  6. Y Wang1,
  7. A Ma1,*,
  8. Z Liu1
  1. 1Department of Cardiovascular Medicine, First Hospital of Xi’an Jiaotong University, Xi’an shaanxi, China
  2. 2Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
  1. Correspondence to:
    Professor Zuyi Yuan
    Department of Cardiovascular Medicine, First Hospital of Xi’an Jiaotong University, No 1 Jiankang Road, Xi’an, Shaanxi 710061, China;


Objective: To test the hypothesis that activation of peroxisome proliferator activated receptor γ (PPAR-γ) reduces experimental autoimmune myocarditis (EAM) associated with inhibitor κB (IκB) α induction, blockade of nuclear factor κB (NF-κB), and inhibition of inflammatory cytokine expression.

Methods: EAM was induced in Lewis rats by immunisation with porcine cardiac myosin. PPAR-γ activators 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) and pioglitazone (PIO) were administered to rats with EAM.

Results: Enhanced PPAR-γ expression was prominently stained in the nuclear and perinuclear regions of infiltrating inflammatory cells. Administration of 15d-PGJ2 and PIO greatly reduced the severity of myocarditis and suppressed myocardial mRNA and protein expression of inflammatory cytokines in rats with EAM. In addition, treatment with PPAR-γ activators enhanced IκB concentrations in the cytoplasmic fractions and nuclear fractions from inflammatory myocardium. Concurrently, NF-κB was greatly activated in myocarditis; this activation was blocked in the 15d-PGJ2 treated and PIO treated groups.

Conclusions: PPAR-γ may have a role in the pathophysiology of EAM. Because an increase in IκB expression and inhibition of translocation of the NF-κB subunit p65 to the nucleus in inflammatory cells correlated with the protective effects of PPAR-γ activators, these results suggest that PPAR-γ activators act sequentially through PPAR-γ activation, IκB induction, blockade of NF-κB activation, and inhibition of inflammatory cytokine expression. These results suggest that PPAR-γ activators such as 15d-PGJ2 and PIO may have the potential to modulate human inflammatory heart diseases such as myocarditis.

  • 15d-PGJ2, 15-deoxy-Δ12,14-prostaglandin J2
  • EAM, experimental autoimmune myocarditis
  • IL, interleukin
  • NF-κB, nuclear factor κB
  • PBS, phosphate buffered saline
  • PIO, pioglitazone
  • PPAR-γ, peroxisome proliferator activated receptor γ
  • TNF-α, tumour necrosis factor α
  • myocarditis
  • immunity
  • PPAR-γ
  • NF-κB
  • cytokine
  • inflammation

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  • * Also the Key Laboratory of Environment and Genes Related to Diseases, Xi’an Jiaotong University, Ministry of Education of China, Xi’an shaanxi, China

  • Published Online First 17 March 2005

  • Supported in part by the Natural Science Foundation of China (30170371).