© 2000 by European Society of Cardiology
Copyright © 2000, European Society of Cardiology
Alterations in Ca2+ cycling proteins and G
q signaling after left ventricular assist device support in failing human hearts
aDepartment of Medicine, Case Western Reserve University and University Hospitals of Cleveland, 11100 Euclid Avenue Cleveland, OH 44106-5029, USA
bUniversity of Utah, Salt Lake City, UT, USA
cUniversity of Cincinnati, Cincinnati, OH, USA
* Corresponding author. Tel.: +1-216-844-3293; fax: +1-216-844-3145 raw19{at}po.cwru.edu
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
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 Gq, phospholipase C β1, regulators of G protein signaling (RGS), sarcoplasmic reticulum Ca2+ ATPase, phospholamban and translocation of protein kinase C isoforms (, β1, and β2). Results: The paired pre- and post- left ventricular assist device samples revealed that RGS2, a selective inhibitor of Gq, was decreased (P<0.01), while the status of Gq, phospholipase C β1, 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 β1 activation may contribute to improved mechanical function produced by left ventricular assist device support in human heart failure.
KEYWORDS G-proteins; Heart failure; Protein kinases; Signal transduction; Transplantation
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. Vanderheyden, W. Mullens, L. Delrue, M. Goethals, B. de Bruyne, W. Wijns, P. Geelen, S. Verstreken, F. Wellens, and J. Bartunek Myocardial Gene Expression in Heart Failure Patients Treated With Cardiac Resynchronization Therapy: Responders Versus Nonresponders J. Am. Coll. Cardiol., January 15, 2008; 51(2): 129 - 136. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. van der Velden, N. A. Narolska, R. R. Lamberts, N. M. Boontje, A. Borbely, R. Zaremba, J. G.F. Bronzwaer, Z. Papp, K. Jaquet, W. J. Paulus, et al. Functional effects of protein kinase C-mediated myofilament phosphorylation in human myocardium Cardiovasc Res, March 1, 2006; 69(4): 876 - 887. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. L. Riddle, R. A. Schwartzman, M. Bond, and P. A. Insel Multi-Tasking RGS Proteins in the Heart: The Next Therapeutic Target? Circ. Res., March 4, 2005; 96(4): 401 - 411. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. T. Gan, V. Rajapurohitam, J. V. Haist, P. Chidiac, M. A. Cook, and M. Karmazyn Inhibition of Phenylephrine-Induced Cardiomyocyte Hypertrophy by Activation of Multiple Adenosine Receptor Subtypes J. Pharmacol. Exp. Ther., January 1, 2005; 312(1): 27 - 34. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Hall, S. Grindle, X. Han, D. Fermin, S. Park, Y. Chen, R. J. Bache, A. Mariash, Z. Guan, S. Ormaza, et al. Genomic profiling of the human heart before and after mechanical support with a ventricular assist device reveals alterations in vascular signaling networks Physiol Genomics, May 19, 2004; 17(3): 283 - 291. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. K. F. Hon and M. H. Yacoub Bridge to recovery with the use of left ventricular assist device and clenbuterol Ann. Thorac. Surg., June 1, 2003; 75(90060): S36 - 41. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Chen, V. Piacentino III, S. Furukawa, B. Goldman, K. B. Margulies, and S. R. Houser L-Type Ca2+ Channel Density and Regulation Are Altered in Failing Human Ventricular Myocytes and Recover After Support With Mechanical Assist Devices Circ. Res., September 20, 2002; 91(6): 517 - 524. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Hollinger and J. R. Hepler Cellular Regulation of RGS Proteins: Modulators and Integrators of G Protein Signaling Pharmacol. Rev., September 1, 2002; 54(3): 527 - 559. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Mittmann, C. H. Chung, G. Hoppner, C. Michalek, M. Nose, C. Schuler, A. Schuh, T. Eschenhagen, J. Weil, B. Pieske, et al. Expression of ten RGS proteins in human myocardium: functional characterization of an upregulation of RGS4 in heart failure Cardiovasc Res, September 1, 2002; 55(4): 778 - 786. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Takeishi, Q. Huang, J.-i. Abe, W. Che, J.-D. Lee, H. Kawakatsu, B. D Hoit, Bradford.C Berk, and R. A Walsh Activation of mitogen-activated protein kinases and p90 ribosomal S6 kinase in failing human hearts with dilated cardiomyopathy Cardiovasc Res, January 1, 2002; 53(1): 131 - 137. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. L. Ogletree-Hughes, L. B. Stull, W. E. Sweet, N. G. Smedira, P. M. McCarthy, and C. S. Moravec Mechanical Unloading Restores {beta}-Adrenergic Responsiveness and Reverses Receptor Downregulation in the Failing Human Heart Circulation, August 21, 2001; 104(8): 881 - 886. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. S. Kumpati, P. M. McCarthy, and K. J. Hoercher Left ventricular assist device bridge to recovery: a review of the current status Ann. Thorac. Surg., March 1, 2001; 71 (2007): S103 - S108. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Z. Feuerstein and D. Rozanski G Proteins and Heart Failure : Is G{alpha}q a Novel Target for Heart Failure? Circ. Res., December 8, 2000; 87(12): 1085 - 1086. [Full Text] [PDF]
|
|
|
|
|
|
P. M. Heerdt, J. W. Holmes, B. Cai, A. Barbone, J. D. Madigan, S. Reiken, D. L. Lee, M. C. Oz, A. R. Marks, and D. Burkhoff Chronic Unloading by Left Ventricular Assist Device Reverses Contractile Dysfunction and Alters Gene Expression in End-Stage Heart Failure Circulation, November 28, 2000; 102(22): 2713 - 2719. [Abstract] [Full Text] [PDF]
|
|