title: Molecular signature of recovery following combination left ventricular assist device (LVAD) support and pharmacologic therapy.
abstract: OBJECTIVE
  A novel combination therapy consisting of a left ventricular assist device (LVAD) combined with pharmacologic therapy including the selective beta(2)-agonist, clenbuterol, has shown promise in restoring ventricular function in patients with heart failure. The aim of this study was to identify common genes and signalling pathways whose expression was associated with reversal of heart failure and restoration of ventricular function.
  
  
  RESULTS
  Microarray analysis was performed on six paired human heart samples harvested at the time of LVAD implant and at the time of LVAD explant for recovery of ventricular function (post). Follow-up data shows that the improvements in ventricular function have been maintained for an average of 3.8 years post-explant. Analysis of the gene expression data revealed: (i) a significant association of integrin pathway signalling with recovery and (ii) the identification of several novel targets including, EPAC2, in the well-described cAMP pathway whose expression was down-regulated with recovery, and was associated with improvements in cardiac contractility, metabolism, and function.
  
  
  CONCLUSIONS
  This data set represents the first description of signalling pathways associated with the functional recovery of end-stage human heart failure and the identification of new targets in the human heart that are modified by this combination therapy.
authors.affiliation: Lillehei Heart Institute, Division of Cardiology, Department of Medicine, University of Minnesota, Mayo Mail Code 508, 420 Delaware Street SE, Minneapolis, MN 55455, USA. jlhall@umn.edu
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Hall
authors.forename: Emma J
authors.initials: EJ
authors.lastname: Birks
authors.forename: Suzanne
authors.initials: S
authors.lastname: Grindle
authors.forename: Martin E
authors.initials: ME
authors.lastname: Cullen
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Barton
authors.forename: James E
authors.initials: JE
authors.lastname: Rider
authors.forename: Sangjin
authors.initials: S
authors.lastname: Lee
authors.forename: Subash
authors.initials: S
authors.lastname: Harwalker
authors.forename: Ami
authors.initials: A
authors.lastname: Mariash
authors.forename: Neeta
authors.initials: N
authors.lastname: Adhikari
authors.forename: Nathan J
authors.initials: NJ
authors.lastname: Charles
authors.forename: Leanne E
authors.initials: LE
authors.lastname: Felkin
authors.forename: Sean
authors.initials: S
authors.lastname: Polster
authors.forename: Robert S
authors.initials: RS
authors.lastname: George
authors.forename: Leslie W
authors.initials: LW
authors.lastname: Miller
authors.forename: Magdi H
authors.initials: MH
authors.lastname: Yacoub
mesh_terms: D000318:Adrenergic beta-Agonists / Q000627:therapeutic use*; D000328:Adult; D003131:Combined Modality Therapy; D005260:Female; D020869:Gene Expression Profiling; D006333:Heart Failure / Q000235:genetics / Q000628:therapy*; D006353:Heart-Assist Devices; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D020127:Recovery of Function; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
chemical_list: D000318:Adrenergic beta-Agonists