title: Molecular Changes in Children with Heart Failure Undergoing Left Ventricular Assist Device Therapy.
abstract: To determine whether left ventricular assist device (LVAD) treatment in children with heart failure would result in the modification of molecular pathways involved in heart failure pathophysiology.
  
  
  
  Forty-seven explanted hearts from children were studied (16 nonfailing control, 20 failing, and 11 failing post-LVAD implantation [F-LVAD]). Protein expression and phosphorylation states were determined by receptor binding assays and Western blots. mRNA expression was measured with real-time quantitative polymerase chain reaction. To evaluate for interactions and identify correlations, 2-way ANOVA and regression analysis were performed.
  
  
  
  Treatment with LVAD resulted in recovery of total β-adrenergic receptor expression and β1-adrenergic receptor (β1-AR) in failing hearts to normal levels (β-adrenergic receptor expression : 67.2 ± 11.5 fmol/mg failing vs 99.5 ± 27.7 fmol/mg nonfailing, 104 ± 38.7 fmol/mg F-LVAD, P ≤ .01; β1-AR: 52.2 ± 10.3 fmol/mg failing vs 83.0 ± 23 fmol/mg non-failing, 76.5 ± 32.1 fmol/mg F-LVAD P ≤ .03). The high levels of G protein-coupled receptor kinase-2 were returned to nonfailing levels after LVAD treatment (5.6 ± 9.0 failing vs 1.0 ± 0.493 nonfailing, 1.0 ± 1.3 F-LVAD). Interestingly, β2-adrenergic receptor expression was significantly greater in F-LVAD (27.5 ± 12; P < .005) hearts compared with nonfailing (16.4 ± 6.1) and failing (15.1 ± 4.2) hearts. Phospholamban phosphorylation at serine 16 was significantly greater in F-LVAD (7.7 ± 11.7) hearts compared with nonfailing (1.0 ± 1.2, P = .02) and failing (0.8 ± 1.0, P = .01) hearts. Also, atrial natriuretic factor (0.6 ± 0.8) and brain natriuretic peptide (0.1 ± 0.1) expression in F-LVAD was significantly lower compared with failing hearts (2.8 ± 3.6, P = .01 and 0.6 ± 0.7, P = .02).
  
  
  
  LVAD treatment in children with heart failure results in reversal of several pathologic myocellular processes, and G protein-coupled receptor kinase-2 may regulate β1-AR but not β2-adrenergic receptor expression in children with heart failure.
authors.affiliation: Division of Cardiology, Department of Medicine, University of Colorado Denver, Aurora, CO.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Medina
authors.affiliation: Division of Cardiology, Department of Medicine, University of Colorado Denver, Aurora, CO.
authors.forename: Carmen C
authors.initials: CC
authors.lastname: Sucharov
authors.affiliation: Division of Cardiology, Department of Medicine, University of Colorado Denver, Aurora, CO.
authors.forename: Penny
authors.initials: P
authors.lastname: Nelson
authors.affiliation: Department of Pediatrics, University of Colorado School of Medicine, Children's Hospital Colorado, Aurora, CO.
authors.forename: Shelley D
authors.initials: SD
authors.lastname: Miyamoto
authors.affiliation: Division of Cardiology, Department of Medicine, University of Colorado Denver, Aurora, CO; Division of Cardiology, Department of Medicine, Denver Health and Hospital Authority, Denver, CO.
authors.forename: Brian L
authors.initials: BL
authors.lastname: Stauffer
mesh_terms: D000293:Adolescent; D000367:Age Factors; D000704:Analysis of Variance; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D002648:Child; D002675:Child, Preschool; D005260:Female; D054769:G-Protein-Coupled Receptor Kinase 2 / Q000378:metabolism*; D006333:Heart Failure / Q000175:diagnosis / Q000601:surgery*; D006353:Heart-Assist Devices; D006801:Humans; D016014:Linear Models; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D012016:Reference Values; D018570:Risk Assessment; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D014019:Tissue Donors
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; D009320:Atrial Natriuretic Factor; D054769:G-Protein-Coupled Receptor Kinase 2
keywords: pathological gene program; phospholamban; β-adrenergic receptor