title: Sarcomeric genes involved in reverse remodeling of the heart during left ventricular assist device support.
abstract: BACKGROUND
  Left ventricular assist devices (LVADs) implanted in patients with severe congestive heart failure (CHF) as a bridge to transplantation have been shown to reverse chamber enlargement, regress cellular hypertrophy, and increase contractility. The purpose of this study was to gain a better understanding of the molecular changes associated with increased contractility after LVAD support.
  
  
  METHODS
  We took tissue sections from the left ventricular apex of 12 patients with CHF who were undergoing LVAD insertion (pre-LVAD) and from the LV free wall of those same patients before transplantation (post-LVAD). To control for sample-site differences, we obtained samples from the same regions in 7 patients with CHF who were undergoing transplantation without LVAD support and in 4 non- failing donor hearts. Gene expression was then probed on a custom DNA array containing 2,700 cardiac-enriched cDNA clones.
  
  
  RESULTS
  Calcium-handling genes were up-regulated by LVAD support, as previously reported. Sarcomeric genes were the other principle class of genes up-regulated by LVAD support, consistent with a possible restoration of sarcomere structure in reverse ventricular remodeling. However, a decrease in the fibrous component of the myocardium, also potentially involved in reverse remodeling, was not evident at the level of gene transcription because fibroblast markers were either unchanged or up-regulated. The remaining regulated genes did not fall into any defined functional class.
  
  
  CONCLUSIONS
  Changes in the regulation of sarcomeric, calcium-handling, and fibroblast genes during LVAD support indicate a cardiac molecular adaptation to mechanical unloading. These molecular changes may play a role in the observed increase in contractile function during reverse remodeling.
authors.affiliation: Millennium Pharmaceuticals, Cambridge, Massachusetts, USA.
authors.forename: Amélie
authors.initials: A
authors.lastname: Rodrigue-Way
authors.forename: Daniel
authors.initials: D
authors.lastname: Burkhoff
authors.forename: Bard J
authors.initials: BJ
authors.lastname: Geesaman
authors.forename: Serge
authors.initials: S
authors.lastname: Golden
authors.forename: Jian
authors.initials: J
authors.lastname: Xu
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Pollman
authors.forename: Mary
authors.initials: M
authors.lastname: Donoghue
authors.forename: Raju
authors.initials: R
authors.lastname: Jeyaseelan
authors.forename: Steven
authors.initials: S
authors.lastname: Houser
authors.forename: Roger E
authors.initials: RE
authors.lastname: Breitbart
authors.forename: Andrew
authors.initials: A
authors.lastname: Marks
authors.forename: Susan
authors.initials: S
authors.lastname: Acton
mesh_terms: D000328:Adult; D000368:Aged; D009320:Atrial Natriuretic Factor / Q000235:genetics / Q000378:metabolism; D001794:Blood Pressure / Q000235:genetics; D055513:Connective Tissue Growth Factor; D005260:Female; D006333:Heart Failure / Q000235:genetics / Q000601:surgery; D016027:Heart Transplantation; D006352:Heart Ventricles / Q000378:metabolism / Q000601:surgery; D006353:Heart-Assist Devices; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000235:genetics; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism; D020097:Natriuretic Peptide, Brain / Q000235:genetics / Q000378:metabolism; D015676:Osteonectin / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013318:Stroke Volume / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics; D020257:Ventricular Remodeling / Q000235:genetics*
chemical_list: C526317:CCN2 protein, human; D017874:Immediate-Early Proteins; D036341:Intercellular Signaling Peptides and Proteins; D015676:Osteonectin; D012333:RNA, Messenger; D020097:Natriuretic Peptide, Brain; D055513:Connective Tissue Growth Factor; D009320:Atrial Natriuretic Factor; D018995:Myosin Heavy Chains