title: Alterations in Ca2+ cycling proteins and G alpha q signaling after left ventricular assist device support in failing human hearts.
abstract: OBJECTIVE
  Left ventricular assist device support mechanically unloads the failing ventricle with resultant improvement in cardiac geometry and function in patients with end-stage heart failure. Activation of the G alpha q signaling pathway, including protein kinase C, appears to be involved in the progression of heart failure. Similarly down-regulation of Ca2+ cycling proteins may contribute to contractile depression in this clinical syndrome. Thus we examined whether protein kinase C activation and decreased Ca2+ cycling protein levels could be reversed by left ventricular assist device support.
  
  
  METHODS
  Left ventricular myocardial specimens were obtained from seven patients during placement of left ventricular assist device and heart transplantation. We examined changes in protein levels of G alpha q, phospholipase C beta 1, regulators of G protein signaling (RGS), sarcoplasmic reticulum Ca2+ ATPase, phospholamban and translocation of protein kinase C isoforms (alpha, beta 1, and beta 2).
  
  
  RESULTS
  The paired pre- and post-left ventricular assist device samples revealed that RGS2, a selective inhibitor of G alpha q, was decreased (P < 0.01), while the status of G alpha q, phospholipase C beta 1, RGS3 and RGS4 were unchanged after left ventricular assist device implantation. Translocation of protein kinase C isoforms remained unchanged. Left ventricular assist device support increased sarcoplasmic reticulum Ca2+ ATPase protein level (P < 0.01), while phospholamban abundance was unchanged.
  
  
  CONCLUSIONS
  We conclude that altered protein expression and stoichiometry of the major cardiomyocyte Ca2+ cycling proteins rather than reduced phospholipase C beta 1 activation may contribute to improved mechanical function produced by left ventricular assist device support in human heart failure.
authors.affiliation: Department of Medicine, Case Western Reserve University, Cleveland, OH, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Takeishi
authors.forename: T
authors.initials: T
authors.lastname: Jalili
authors.forename: B D
authors.initials: BD
authors.lastname: Hoit
authors.forename: D L
authors.initials: DL
authors.lastname: Kirkpatrick
authors.forename: L E
authors.initials: LE
authors.lastname: Wagoner
authors.forename: W T
authors.initials: WT
authors.lastname: Abraham
authors.forename: R A
authors.initials: RA
authors.lastname: Walsh
mesh_terms: D000293:Adolescent; D000328:Adult; D002135:Calcium-Binding Proteins / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006333:Heart Failure / Q000378:metabolism* / Q000628:therapy; D006353:Heart-Assist Devices; D006801:Humans; D015151:Immunoblotting; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D020710:RGS Proteins / Q000378:metabolism*; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000201:enzymology; D015398:Signal Transduction / Q000502:physiology; D018709:Statistics, Nonparametric; D000099211:Phospholamban
chemical_list: D002135:Calcium-Binding Proteins; D000252:Calcium-Transporting ATPases; D019204:GTP-Binding Proteins; D007527:Isoenzymes; D011493:Protein Kinase C; D020710:RGS Proteins; D000099211:Phospholamban; C105345:Rgs2 protein, mouse