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

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

Research output: Contribution to journalArticle

Abstract

Aims: The G protein-coupled receptor kinase-2 (GRK2 or β-ARK1) regulates β-adrenergic receptors (β-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 β-ARs. Moreover, we were interested in determining whether GRK2 levels in myocardium and lymphocytes may be associated with β-AR dysfunction and HF severity. Methods and results: In myocardial biopsies from explanted failing human hearts, GRK activity was inversely correlated with β-AR-mediated cAMP production (R2 = -0.215, P <0.05, n = 24). Multiple regression analysis confirmed that GRK activity participates with β-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 β-AR responsiveness and appears to increase with disease severity. Therefore, lymphocytes may provide a surrogate for monitoring cardiac GRK2 in human HF.

Original languageEnglish
Pages (from-to)1752-1758
Number of pages7
JournalEuropean Heart Journal
Volume26
Issue number17
DOIs
Publication statusPublished - Sep 2005

Keywords

  • Adrenergic
  • Beta
  • Heart failure
  • Lymphocytes
  • Prognosis
  • Receptors
  • Signal transduction

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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    Iaccarino, G., Barbato, E., Cipolletta, E., De Amicis, V., Margulies, K. B., Leosco, D., Trimarco, B., & Koch, W. J. (2005). Elevated myocardial and lymphocyte GRK2 expression and activity in human heart failure. European Heart Journal, 26(17), 1752-1758. https://doi.org/10.1093/eurheartj/ehi429