Skip Navigation



European Heart Journal Advance Access published online on July 29, 2005
European Heart Journal, doi:10.1093/eurheartj/ehi429
This Article
Right arrow Full Text (Rapid PDF)
Right arrow All Versions of this Article:
26/17/1752    most recent
ehi429v1
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Iaccarino, G.
Right arrow Articles by Koch, W. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Iaccarino, G.
Right arrow Articles by Koch, W. J.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

European Heart Journal © The European Society of Cardiology 2005; all rights reserved
Received January 25, 2005
Revised June 9, 2005
Accepted June 30, 2005

Preclinical research

Elevated myocardial and lymphocyte GRK2 expression and activity in human heart failure

Guido Iaccarino 1, Emanuele Barbato 1, Ersilia Cipolletta 1, Vincenzo De Amicis 1, Kenneth B. Margulies 2, Dario Leosco 1, Bruno Trimarco 1, and Walter J. Koch 3*

1 Department of Medicina Clinica, Scienze Cardiovascolari ed Immunologiche, Federico II University, Via Pansini 5, 80131 Napoli, Italy
2 Department of Medicine (Cardiology), Temple University Medical Center, Philadelphia, PA, USA
3 Department of Medicine, Center for Translational Medicine, Thomas Jefferson University, 1025 Walnut Street, Room 410, Philadelphia, PA 19107, USA

* To whom correspondence should be addressed.
Walter J. Koch, E-mail: walter.koch{at}jefferson.edu


  Abstract

Aims The G protein-coupled receptor kinase-2 (GRK2 or {beta}-ARK1) regulates {beta}-adrenergic receptors ({beta}-ARs) in the heart, and its cardiac expression is elevated in human heart failure (HF). We sought to determine whether myocardial levels and activity of GRK2 could be monitored using white blood cells, which have been used to study cardiac {beta}-ARs. Moreover, we were interested in determining whether GRK2 levels in myocardium and lymphocytes may be associated with {beta}-AR dysfunction and HF severity.

Methods and results In myocardial biopsies from explanted failing human hearts, GRK activity was inversely correlated with {beta}-AR-mediated cAMP production (R2 = -0.215, P < 0.05, n = 24). Multiple regression analysis confirmed that GRK activity participates with {beta}-AR density to regulate catecholamine-sensitive cAMP responses. Importantly, there was a direct correlation between myocardial and lymphocytes GRK2 activity (R2 = 0.5686, P < 0.05, n = 10). Lymphocyte GRK activity was assessed in HF patients with various ejection fractions (EFs) (n = 33), and kinase activity was significantly higher in patients with lower EFs and was higher with increasing NYHA class (P < 0.001).

Conclusion Myocardial GRK2 expression and activity are mirrored by lymphocyte levels of this kinase, and its elevation in HF is associated with the loss of {beta}-AR responsiveness and appears to increase with disease severity. Therefore, lymphocytes may provide a surrogate for monitoring cardiac GRK2 in human HF.

Keywords: Heart failure; Prognosis; Receptors; Adrenergic; Beta; Signal transduction; Lymphocytes.
Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Cardiovasc ResHome page
E. Cipolletta, A. Campanile, G. Santulli, E. Sanzari, D. Leosco, P. Campiglia, B. Trimarco, and G. Iaccarino
The G protein coupled receptor kinase 2 plays an essential role in beta-adrenergic receptor-induced insulin resistance
Cardiovasc Res, December 1, 2009; 84(3): 407 - 415.
[Abstract] [Full Text] [PDF]

Home page
 HypertensionHome page
H. I. Cohn, Y. Xi, S. Pesant, D. M. Harris, T. Hyslop, B. Falkner, and A. D. Eckhart
G Protein-Coupled Receptor Kinase 2 Expression and Activity Are Associated With Blood Pressure in Black Americans
Hypertension, July 1, 2009; 54(1): 71 - 76.
[Abstract] [Full Text] [PDF]

Home page
 Ann. Thorac. Surg.Home page
C. F. Bulcao, P. K. Pandalai, K. M. D'Souza, W. H. Merrill, and S. A. Akhter
Uncoupling of Myocardial {beta}-Adrenergic Receptor Signaling During Coronary Artery Bypass Grafting: The Role of GRK2
Ann. Thorac. Surg., October 1, 2008; 86(4): 1189 - 1194.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
P. W. Raake, L. E. Vinge, E. Gao, M. Boucher, G. Rengo, X. Chen, B. R. DeGeorge Jr, S. Matkovich, S. R. Houser, P. Most, et al.
G Protein-Coupled Receptor Kinase 2 Ablation in Cardiac Myocytes Before or After Myocardial Infarction Prevents Heart Failure
Circ. Res., August 15, 2008; 103(4): 413 - 422.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
D. Leosco, G. Rengo, G. Iaccarino, L. Golino, M. Marchese, F. Fortunato, C. Zincarelli, E. Sanzari, M. Ciccarelli, G. Galasso, et al.
Exercise promotes angiogenesis and improves {beta}-adrenergic receptor signalling in the post-ischaemic failing rat heart
Cardiovasc Res, May 1, 2008; 78(2): 385 - 394.
[Abstract] [Full Text] [PDF]

Home page
 J Am Coll CardiolHome page
W.H. W. Tang and G. S. Francis
The Year in Heart Failure
J. Am. Coll. Cardiol., December 11, 2007; 50(24): 2344 - 2351.
[Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
D. Leosco, G. Rengo, G. Iaccarino, A. Filippelli, A. Lymperopoulos, C. Zincarelli, F. Fortunato, L. Golino, M. Marchese, G. Esposito, et al.
Exercise training and beta-blocker treatment ameliorate age-dependent impairment of beta-adrenergic receptor signaling and enhance cardiac responsiveness to adrenergic stimulation
Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1596 - H1603.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
W.H. Wilson Tang, G. S. Francis, D. A. Morrow, L. K. Newby, C. P. Cannon, R. L. Jesse, A. B. Storrow, R. H. Christenson, COMMITTEE MEMBERS, R. H. Christenson, et al.
National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines: Clinical Utilization of Cardiac Biomarker Testing in Heart Failure
Circulation, July 31, 2007; 116(5): e99 - e109.
[Full Text] [PDF]

Home page
 HeartHome page
J. Nunez, E. Nunez, L. Consuegra, J. Sanchis, V. Bodi, A. Martinez-Brotons, V. Bertomeu-Gonzalez, R. Robles, M. J Bosch, L. Facila, et al.
Carbohydrate antigen 125: an emerging prognostic risk factor in acute heart failure?
Heart, June 1, 2007; 93(6): 716 - 721.
[Abstract] [Full Text] [PDF]

Home page
 J. Thorac. Cardiovasc. Surg.Home page
P. K. Pandalai, C. F. Bulcao, W. H. Merrill, and S. A. Akhter
Restoration of myocardial {beta}-adrenergic receptor signaling after left ventricular assist device support
J. Thorac. Cardiovasc. Surg., May 1, 2006; 131(5): 975 - 980.
[Abstract] [Full Text] [PDF]

Home page
 Eur Heart JHome page
S. B. Liggett
Lymphocyte GRK levels as biomarkers in heart failure
Eur. Heart J., September 1, 2005; 26(17): 1695 - 1696.
[Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.