title: Cardioprotective effects of peroxisome proliferator activated receptor gamma activators on acute myocarditis: anti-inflammatory actions associated with nuclear factor kappaB blockade.
abstract: OBJECTIVE
  To test the hypothesis that activation of peroxisome proliferator activated receptor gamma (PPAR-gamma) reduces experimental autoimmune myocarditis (EAM) associated with inhibitor kappaB (IkappaB) alpha induction, blockade of nuclear factor kappaB (NF-kappaB), 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 J2 (15d-PGJ2) 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-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-gamma activators enhanced IkappaB concentrations in the cytoplasmic fractions and nuclear fractions from inflammatory myocardium. Concurrently, NF-kappaB was greatly activated in myocarditis; this activation was blocked in the 15d-PGJ2 treated and PIO treated groups.
  
  
  CONCLUSIONS
  PPAR-gamma may have a role in the pathophysiology of EAM. Because an increase in IkappaB expression and inhibition of translocation of the NF-kappaB 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, IkappaB induction, blockade of NF-kappaB activation, and inhibition of inflammatory cytokine expression. These results suggest that PPAR-gamma activators such as 15d-PGJ2 and PIO may have the potential to modulate human inflammatory heart diseases such as myocarditis.
authors.affiliation: Department of Cardiovascular Medicine, First Hospital of Xi'an Jiaotong University, No 1 Jiankang Road, Xi'an, Shaanxi 710061, China. zuyiyuan@mail.xjtu.edu.cn
authors.forename: Z
authors.initials: Z
authors.lastname: Yuan
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: C
authors.initials: C
authors.lastname: Kishimoto
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: A
authors.initials: A
authors.lastname: Ma
authors.forename: Z
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000208:Acute Disease; D000818:Animals; D001327:Autoimmune Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D009205:Myocarditis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D009218:Myosins; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism*; D000077205:Pioglitazone; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000627:therapeutic use; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011917:Rats, Inbred Lew; D045162:Thiazolidinediones / Q000627:therapeutic use
chemical_list: C477819:15-deoxyprostaglandin J2; D002316:Cardiotonic Agents; D016207:Cytokines; D016328:NF-kappa B; D047495:PPAR gamma; D012333:RNA, Messenger; D045162:Thiazolidinediones; D009218:Myosins; D015230:Prostaglandin D2; D000077205:Pioglitazone