title: Molecular signatures of end-stage heart failure.
abstract: BACKGROUND
  To date, gene expression studies related to chronic heart failure (CHF) have mainly involved microarray analysis of myocardial tissues. The potential utility of blood to infer the etiology, pathogenesis, and course of CHF remains unclear. Further, the use of proteomic and metabolomic platforms for molecular profiling of CHF is relatively unexplored.
  
  
  METHODS
  Microarray genomic, iTRAQ proteomic, and nuclear magnetic resonance metabolomic analyses were carried out on blood samples from 29 end-stage CHF patients (16 ischemic heart disease [IHD], 13 nonischemic cardiomyopathy [NICM]), and 20 normal cardiac function (NCF) controls. Robust statistical tests and bioinformatical tools were applied to identify and compare the molecular signatures among these subject groups.
  
  
  RESULTS
  No genes or proteins, and only two metabolites, were differentially expressed between IHD and NICM patients at end stage. However, CHF versus NCF comparison revealed differential expression of 7,426 probe sets, 71 proteins, and 8 metabolites. Functional enrichment analyses of the CHF versus NCF results revealed several in-common biological themes and potential mechanisms underlying advanced heart failure.
  
  
  CONCLUSIONS
  Multiple "-omic" analyses support the convergence of dramatic changes in molecular processes underlying IHD and NICM at end stage.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Lin
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Hollander
authors.forename: Anna
authors.initials: A
authors.lastname: Meredith
authors.forename: Ellamae
authors.initials: E
authors.lastname: Stadnick
authors.forename: Mayu
authors.initials: M
authors.lastname: Sasaki
authors.forename: Gabriela
authors.initials: G
authors.lastname: Cohen Freue
authors.forename: Pooran
authors.initials: P
authors.lastname: Qasimi
authors.forename: Alice
authors.initials: A
authors.lastname: Mui
authors.forename: Raymond T
authors.initials: RT
authors.lastname: Ng
authors.forename: Robert
authors.initials: R
authors.lastname: Balshaw
authors.forename: Janet E
authors.initials: JE
authors.lastname: Wilson-McManus
authors.forename: David
authors.initials: D
authors.lastname: Wishart
authors.forename: David
authors.initials: D
authors.lastname: Hau
authors.forename: Paul A
authors.initials: PA
authors.lastname: Keown
authors.forename: Robert
authors.initials: R
authors.lastname: McMaster
authors.forename: Bruce M
authors.initials: BM
authors.lastname: McManus
mesh_terms: D000328:Adult; D000368:Aged; D009202:Cardiomyopathies / Q000097:blood / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020869:Gene Expression Profiling; D006333:Heart Failure / Q000097:blood / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D040901:Proteomics; D012720:Severity of Illness Index