title: Proteomic and transcriptomic analysis of heart failure due to volume overload in a rat aorto-caval fistula model provides support for new potential therapeutic targets - monoamine oxidase A and transglutaminase 2.
abstract: BACKGROUND
  Chronic hemodynamic overloading leads to heart failure (HF) due to incompletely understood mechanisms. To gain deeper insight into the molecular pathophysiology of volume overload-induced HF and to identify potential markers and targets for novel therapies, we performed proteomic and mRNA expression analysis comparing myocardium from Wistar rats with HF induced by a chronic aorto-caval fistula (ACF) and sham-operated rats harvested at the advanced, decompensated stage of HF.
  
  
  METHODS
  We analyzed control and failing myocardium employing iTRAQ labeling, two-dimensional peptide separation combining peptide IEF and nano-HPLC with MALDI-MS/MS. For the transcriptomic analysis we employed Illumina RatRef-12v1 Expression BeadChip.
  
  
  RESULTS
  In the proteomic analysis we identified 2030 myocardial proteins, of which 66 proteins were differentially expressed. The mRNA expression analysis identified 851 differentially expressed mRNAs.
  
  
  CONCLUSIONS
  The differentially expressed proteins confirm a switch in the substrate preference from fatty acids to other sources in the failing heart. Failing hearts showed downregulation of the major calcium transporters SERCA2 and ryanodine receptor 2 and altered expression of creatine kinases. Decreased expression of two NADPH producing proteins suggests a decreased redox reserve. Overexpression of annexins supports their possible potential as HF biomarkers. Most importantly, among the most up-regulated proteins in ACF hearts were monoamine oxidase A and transglutaminase 2 that are both potential attractive targets of low molecular weight inhibitors in future HF therapy.
authors.affiliation: Institute of Pathological Physiology, First Faculty of Medicine, Charles University, Prague, Czech Republic. jpetr@lf1.cuni.cz.
authors.forename: Jiri
authors.initials: J
authors.lastname: Petrak
authors.forename: Jana
authors.initials: J
authors.lastname: Pospisilova
authors.forename: Miroslava
authors.initials: M
authors.lastname: Sedinova
authors.forename: Petr
authors.initials: P
authors.lastname: Jedelsky
authors.forename: Lucie
authors.initials: L
authors.lastname: Lorkova
authors.forename: Ondrej
authors.initials: O
authors.lastname: Vit
authors.forename: Michal
authors.initials: M
authors.lastname: Kolar
authors.forename: Hynek
authors.initials: H
authors.lastname: Strnad
authors.forename: Jan
authors.initials: J
authors.lastname: Benes
authors.forename: David
authors.initials: D
authors.lastname: Sedmera
authors.forename: Ludek
authors.initials: L
authors.lastname: Cervenka
authors.forename: Vojtech
authors.initials: V
authors.lastname: Melenovsky
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