title: Proteomic profiling of the human failing heart after left ventricular assist device support.
abstract: BACKGROUND
  Left ventricular assist device (LVAD) support is commonly used in patients with heart failure as a bridge to heart transplantation. Whereas myocardial gene expression profile changes have been well established after LVAD support, the consequences on the protein level largely remain unclear.
  
  
  METHODS
  Pre-LVAD and post-LVAD myocardial tissue specimens from dilated cardiomyopathy (DCM) and ischemic heart disease (IHD) patients were analyzed by fluorescent 2-dimensional difference gel electrophoresis, and differentially expressed proteins were identified by mass spectrometry.
  
  
  RESULTS
  In the DCM group, 16 proteins were detected that showed statistically significant downregulation from pre-LVAD to post-LVAD tissue. In IHD patients, 50 alterations were found, including upregulated (n = 12) and downregulated (n = 38) proteins. The identified proteins in both groups partially overlapped and included proteins from cytoskeleton and mitochondrial energy metabolism. The latter changes were paralleled by severe abnormalities in mitochondrial morphology, as shown by electron microscopy. Post-LVAD proteomes of both DCM and IHD patients largely mimicked the protein profiles of non-failing hearts. Downregulation of the serine protease inhibitor α-1-antichymotrypsin in both DCM and IHD patients after LVAD support was confirmed by immunosorbent assay.
  
  
  CONCLUSIONS
  LVAD-induced cardiac remodeling in DCM and IHD patients is associated with downregulation of α-1-antichymotrypsin and specific atrophic changes in protein expression profiles predominantly involved in cytoskeleton integrity and mitochondrial energy metabolism.
authors.affiliation: Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Roel A
authors.initials: RA
authors.lastname: de Weger
authors.forename: Marguerite E I
authors.initials: ME
authors.lastname: Schipper
authors.forename: Erica
authors.initials: E
authors.lastname: Siera-de Koning
authors.forename: Petra
authors.initials: P
authors.lastname: van der Weide
authors.forename: Matthijs F M
authors.initials: MF
authors.lastname: van Oosterhout
authors.forename: Razi
authors.initials: R
authors.lastname: Quadir
authors.forename: Helga
authors.initials: H
authors.lastname: Steenbergen-Nakken
authors.forename: Jaap R
authors.initials: JR
authors.lastname: Lahpor
authors.forename: Nicolaas
authors.initials: N
authors.lastname: de Jonge
authors.forename: Niels
authors.initials: N
authors.lastname: Bovenschen
mesh_terms: D000328:Adult; D002311:Cardiomyopathy, Dilated / Q000378:metabolism / Q000628:therapy; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004734:Energy Metabolism / Q000502:physiology; D005260:Female; D020869:Gene Expression Profiling; D006333:Heart Failure / Q000378:metabolism* / Q000628:therapy*; D006353:Heart-Assist Devices; D006801:Humans; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000378:metabolism; D017202:Myocardial Ischemia / Q000378:metabolism / Q000628:therapy; D020543:Proteome / Q000378:metabolism*; D012189:Retrospective Studies; D000514:alpha 1-Antichymotrypsin / Q000378:metabolism
chemical_list: D003598:Cytoskeletal Proteins; D024101:Mitochondrial Proteins; D020543:Proteome; D000514:alpha 1-Antichymotrypsin