Copyright © 2005, European Society of Cardiology
G-protein-coupled receptor kinase activity in human heart failure: Effects of β-adrenoceptor blockade
aDepartments of Pathophysiology and Nephrology, University of Essen School of Medicine, Hufelandstr. 55, D-45147 Essen, Germany
bClinic for Cardio-Thoracic Surgery, University of Essen School of Medicine, Hufelandstr. 55, D-45147 Essen, Germany
* Corresponding author. Tel.: +49 201 723 4457; fax: +49 201 723 5963. Email address: kirsten.leineweber{at}uni-essen.de
Objectives: In human end-stage heart failure as well as in experimental animal models of heart failure, G-protein-coupled receptor kinase activity (GRK) is increased while β-adrenoceptor responsiveness is diminished. In animal studies, β-adrenoceptor blockers reverse the GRK-mediated desensitization and down-regulation of myocardial β-adrenoceptors. The aim of this study was to investigate whether alterations in GRK activity are an early or late accompaniment of human heart failure and whether also in humans β-adrenoceptor blocker treatment is able to influence myocardial GRK activity.
Methods: We assessed in right atria, obtained from patients at different stages of heart failure, treated with or not treated with β-adrenoceptor blockers, and in the four chambers of explanted hearts, obtained from patients with end-stage heart failure, β-adrenoceptor density (by (-)-[125I]-iodocyanopindolol binding) and GRK activity (by an in vitro rhodopsin phosphorylation assay).
Results: With increasing severity of heart failure, plasma noradrenaline levels increased while myocardial β-adrenoceptor density decreased with a maximum in GRK activity in end-stage heart failure. However, in relation to the progression of heart failure, we found that GRK activity transiently increased at an early stage of heart failure (NYHA I and II) but decreased back to control values in patients at NYHA III and IV. β-Adrenoceptor blockers were able to reduce the early increase in GRK activity at NYHA I and II to control levels, whereas in those patients who did not have increased GRK activity (NYHA III and IV), they had only a marginal effect.
Conclusion: According to our results, an increase in GRK activity is an early and transient event in the course of heart failure that can be prevented by β-adrenoceptor blocker treatment.
KEYWORDS β-Adrenoceptor; Heart failure; β-Arrestins
Time for primary review 20 days
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  U. H. Frey, M. Adamzik, E. Kottenberg-Assenmacher, H. Jakob, I. Manthey, M. Broecker-Preuss, L. Bergmann, G. Heusch, W. Siffert, J. Peters, et al. A novel functional haplotype in the human GNAS gene alters G{alpha}s expression, responsiveness to {beta}-adrenoceptor stimulation, and peri-operative cardiac performance Eur. Heart J., June 1, 2009; 30(11): 1402 - 1410. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Davis, M. V. Westfall, D. Townsend, M. Blankinship, T. J. Herron, G. Guerrero-Serna, W. Wang, E. Devaney, and J. M. Metzger Designing Heart Performance by Gene Transfer Physiol Rev, October 1, 2008; 88(4): 1567 - 1651. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Penela, C. Murga, C. Ribas, A. S. Tutor, S. Peregrin, and F. Mayor Jr. Mechanisms of regulation of G protein-coupled receptor kinases (GRKs) and cardiovascular disease Cardiovasc Res, January 1, 2006; 69(1): 46 - 56. [Abstract] [Full Text] [PDF]
|
|