title: Proteomic analysis identifies mitochondrial metabolic enzymes as major discriminators between different stages of the failing human myocardium.
abstract: OBJECTIVE
  Our aim was to identify patterns in differentially regulated proteins associated with the progression of chronic heart failure. We specifically studied proteomics in chronic reversibly (RDM) and irreversibly dysfunctional myocardium (IRDM), as well as end-stage failing myocardium (ESFM).
  
  
  METHODS
  We studied biopsies from 9 patients with stable chronic heart failure undergoing coronary artery bypass surgery (CABG) (EF 34% +/- 3%) and from 4 patients with ESFM undergoing heart transplantation (EF 17% +/- 5%). In CABG patients paired echocardiographic studies before and 6 months after revascularization classified dysfunctional myocardium as RDM or IRDM. Regions with preserved contractile function served as control. We used two-dimensional gel electrophoresis (2D-PAGE) and computerized image analysis to investigate myocardial protein expression. Proteins were identified by in-gel digestion and subsequent liquid chromatography-tandem mass spectrometry (LC-MS/MS).
  
  
  RESULTS
  Among 3 significantly altered protein spots in RDM we identified 2 up-regulated glycolytic enzymes. In IRDM 15 proteins were signficantly altered of which we identified 10, among these 6 were down-regulated mitochondrial enzymes. In ESFM 9 of 12 significantly altered protein spots were identified. Six were down-regulated mitochondrial enzymes.
  
  
  CONCLUSIONS
  Myocardial metabolism may be involved in the progression of heart failure to irreversible dysfunction and end-stage heart failure.
authors.affiliation: Institute of Medical Biochemistry, University of Aarhus, Denmark.
authors.forename: Sigitas
authors.initials: S
authors.lastname: Urbonavicius
authors.forename: Henrik
authors.initials: H
authors.lastname: Wiggers
authors.forename: Hans Erik
authors.initials: HE
authors.lastname: Bøtker
authors.forename: Torsten Toftegaard
authors.initials: TT
authors.lastname: Nielsen
authors.forename: Hans Henrik
authors.initials: HH
authors.lastname: Kimose
authors.forename: Morten
authors.initials: M
authors.lastname: Østergaard
authors.forename: Jes S
authors.initials: JS
authors.lastname: Lindholt
authors.forename: Henrik
authors.initials: H
authors.lastname: Vorum
authors.forename: Bent
authors.initials: B
authors.lastname: Honoré
mesh_terms: D002853:Chromatography, Liquid; D002908:Chronic Disease; D015536:Down-Regulation; D015180:Electrophoresis, Gel, Two-Dimensional; D006333:Heart Failure / Q000201:enzymology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000201:enzymology*; D009206:Myocardium / Q000378:metabolism*; D040901:Proteomics; D053719:Tandem Mass Spectrometry; D015854:Up-Regulation