Reduction of lymphocyte G protein-coupled receptor kinase-2 (GRK2) after exercise training predicts survival in patients with heart failure

Giuseppe Rengo, Gennaro Galasso, Grazia D. Femminella, Valentina Parisi, Carmela Zincarelli, Gennaro Pagano, Claudio de Lucia, Alessandro Cannavo, Daniela Liccardo, Caterina Marciano, Carlo Vigorito, Francesco Giallauria, Nicola Ferrara, Giuseppe Furgi, Pasquale Perrone Filardi, Walter J. Koch, Dario Leosco

Research output: Contribution to journalArticlepeer-review


Background: Increased cardiac G protein-coupled receptor kinase-2 (GRK2) expression has a pivotal role at inducing heart failure (HF)-related b-adrenergic receptor (βAR) dysfunction. Importantly, abnormalities of βAR signalling in the failing heart, including GRK2 overexpression, are mirrored in circulating lymphocytes and correlate with HF severity. Exercise training has been shown to exert several beneficial effects on the failing heart, including normalization of cardiac βAR function and GRK2 protein levels. In the present study, we evaluated whether lymphocyte GRK2 levels and shortterm changes of this kinase after an exercise training programme can predict long-term survival in HF patients. Methods: For this purpose, we prospectively studied 193 HF patients who underwent a 3-month exercise training programme. Lymphocyte GRK2 protein levels, plasma N-terminal pro-brain natriuretic peptide, and norepinephrine were measured at baseline and after training along with clinical and functional parameters (left ventricular ejection fraction, NYHA class, and peak-VO2). Cardiac-related mortality was evaluated during a mean follow-up period of 37±20 months. Results: Exercise was associated with a significant reduction of lymphocyte GRK2 protein levels (from 1.29±0.52 to 1.16±0.65 densitometric units, p≥0.0001). Importantly, exercise related changes of GRK2 (delta values) robustly predicted survival in our study population. Interestingly, HF patients who did not show reduced lymphocyte GRK2 protein levels after training presented the poorest outcome. Conclusions: Our data offer the first demonstration that changes of lymphocyte GRK2 after exercise training can strongly predict outcome in advanced HF.

Original languageEnglish
Pages (from-to)4-11
Number of pages8
JournalEuropean Journal of Preventive Cardiology
Issue number1
Publication statusPublished - Jan 2014


  • β-Adrenergic receptor
  • biomarker
  • exercise training
  • G protein-coupled receptor kinase-2
  • heart failure

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Epidemiology


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