Cardioprotective effects of peroxisome proliferator activated receptor γ activators on acute myocarditis:: anti-inflammatory actions associated with nuclear factor κB blockade

被引:30
作者
Yuan, Z
Liu, Y
Liu, Y
Zhang, J
Kishimoto, C
Wang, Y
Ma, A
Liu, Z
机构
[1] Xi An Jiao Tong Univ, Hosp 1, Dept Cardiovasc Med, Xian 710061, Peoples R China
[2] Kyoto Univ, Grad Sch Med, Dept Cardiovasc Med, Kyoto, Japan
[3] Xi An Jiao Tong Univ, Minist Educ China, Key LabEnvironm & Genes Related Dis, Xian, Peoples R China
关键词
D O I
10.1136/hrt.2004.046292
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective: To test the hypothesis that activation of peroxisome proliferator activated receptor gamma (PPAR-gamma) reduces experimental autoimmune myocarditis (EAM) associated with inhibitor kappa B (I kappa B) alpha induction, blockade of nuclear factor kappa B (NF-kappa B), and inhibition of inflammatory cytokine expression. Methods: EAM was induced in Lewis rats by immunisation with porcine cardiac myosin. PPAR-gamma activators 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d- PGJ(2)) and pioglitazone (PIO) were administered to rats with EAM. Results: Enhanced PPAR-gamma expression was prominently stained in the nuclear and perinuclear regions of infiltrating inflammatory cells. Administration of 15d- PGJ(2) 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-gamma activators enhanced I kappa B concentrations in the cytoplasmic fractions and nuclear fractions from inflammatory myocardium. Concurrently, NF-kappa B was greatly activated in myocarditis; this activation was blocked in the 15d-PGJ(2) treated and PIO treated groups. Conclusions: PPAR-gamma may have a role in the pathophysiology of EAM. Because an increase in I kappa B expression and inhibition of translocation of the NF-kappa B subunit p65 to the nucleus in inflammatory cells correlated with the protective effects of PPAR-gamma activators, these results suggest that PPAR-gamma activators act sequentially through PPAR-gamma activation, I kappa B induction, blockade of NF-kappa B activation, and inhibition of inflammatory cytokine expression. These results suggest that PPAR-gamma activators such as 15d- PGJ(2) and PIO may have the potential to modulate human inflammatory heart diseases such as myocarditis.
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页码:1203 / 1208
页数:6
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