title: Single-dose GSTP1 prevents infarction-induced heart failure.
abstract: BACKGROUND
  Heart failure (HF) is a common and often fatal complication of myocardial infarction (MI). Glutathione S-transferase P1-1 (GSTP1) has antiapoptotic and antiinflammatory effects and is a specific serum marker in HF patients. However, its role in HF treatment is unknown.
  
  
  RESULTS
  GSTP1 effect was examined in a rat MI-induced HF model. Magnetic resonance imaging was used to examine cardiac function. GSTP1 and tumor necrosis factor α receptor-associated factor 2 (TRAF2) mRNA and protein expression were elevated in failing myocardium, although GSTP-1 binding activity to TRAF2 was not changed versus control. HF was associated with higher active JNK1 and p38 protein expression but reduced GSTP-1 binding activity to JNK1 and p38. Recombinant GSTP1 inhibited JNK1 and p38 and enhanced its own binding activity to TRAF2 and JNK1 in vitro. In the HF model, single-dose GSTP1 treatment reduced infarct area, apoptosis, and the expression of JNK1, p38, nuclear factor κB, and proinflammatory cytokines and improved thinning ratio, cardiac index and output, stroke volume, ejection fraction, regional wall motion, and survival compared with control.
  
  
  CONCLUSIONS
  GSTP1 application early after MI results in long-term beneficial structural and functional effects that prevent progression to HF. GSTP1 could be a novel adjunct myocardial salvage approach in patients after MI.
authors.affiliation: Biomedical Sciences, University of Veterinary Medicine, Vienna, Austria.
authors.forename: Olena
authors.initials: O
authors.lastname: Andrukhova
authors.affiliation: Department of Cardiac Surgery, Medical University of Vienna, Vienna, Austria; Department of Cardiovascular Research, Medical University of Vienna, Vienna, Austria.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Salama
authors.affiliation: Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Krssak
authors.affiliation: Department of Cardiac Surgery, Medical University of Vienna, Vienna, Austria.
authors.forename: Dominik
authors.initials: D
authors.lastname: Wiedemann
authors.affiliation: Department of Cardiovascular Research, Medical University of Vienna, Vienna, Austria.
authors.forename: Lamia
authors.initials: L
authors.lastname: El-Housseiny
authors.affiliation: Department of Nuclear Medicine, University of Munich, Munich, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Hacker
authors.affiliation: Department of Nuclear Medicine, University of Munich, Munich, Germany.
authors.forename: Franz J
authors.initials: FJ
authors.lastname: Gildehaus
authors.affiliation: Central Research Unit, Bernhard Gottlieb School of Dentistry, Medical University of Vienna, Vienna, Austria.
authors.forename: Oleh
authors.initials: O
authors.lastname: Andrukhov
authors.affiliation: Department of Nuclear Medicine, Wilhelminen Hospital, Vienna, Austria.
authors.forename: Siroos
authors.initials: S
authors.lastname: Mirzaei
authors.affiliation: Department of Cardiac Surgery, Medical University of Vienna, Vienna, Austria.
authors.forename: Alfred
authors.initials: A
authors.lastname: Kocher
authors.affiliation: Department of Cardiac Surgery, Medical University of Vienna, Vienna, Austria. Electronic address: andreas.zuckermann@meduniwien.ac.at.
authors.forename: Andreas
authors.initials: A
authors.lastname: Zuckermann
authors.affiliation: Department of Cardiac Surgery, Medical University of Vienna, Vienna, Austria; Department of Cardiovascular Research, Medical University of Vienna, Vienna, Austria.
authors.forename: Seyedhossein
authors.initials: S
authors.lastname: Aharinejad
mesh_terms: D000818:Animals; D002316:Cardiotonic Agents / Q000008:administration & dosage*; D002478:Cells, Cultured; D018450:Disease Progression; D005260:Female; D051549:Glutathione S-Transferase pi / Q000008:administration & dosage*; D006333:Heart Failure / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D051381:Rats
chemical_list: D002316:Cardiotonic Agents; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi
keywords: GSTP1; Heart failure; myocardial infarction; treatment