Impact of diabetes mellitus on lymphocyte GRK2 protein levels in patients with heart failure
Giuseppe Rengo
IRCCS, Scientific Institute of Telese Terme (BN), Salvatore Maugeri Foundation, Telese Terme, Italy
Search for more papers by this authorGennaro Pagano
Department of Medicine and Health Sciences, University of Molise, Campobasso, Italy
Department of Translational Medical Sciences, Federico II University, Naples, Italy
Search for more papers by this authorStefania Paolillo
Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy
Search for more papers by this authorClaudio de Lucia
Department of Translational Medical Sciences, Federico II University, Naples, Italy
Search for more papers by this authorGrazia D. Femminella
Department of Translational Medical Sciences, Federico II University, Naples, Italy
Search for more papers by this authorDaniela Liccardo
Department of Translational Medical Sciences, Federico II University, Naples, Italy
Search for more papers by this authorAlessandro Cannavo
Department of Translational Medical Sciences, Federico II University, Naples, Italy
Search for more papers by this authorRoberto Formisano
Department of Translational Medical Sciences, Federico II University, Naples, Italy
Search for more papers by this authorLaura Petraglia
Department of Translational Medical Sciences, Federico II University, Naples, Italy
Search for more papers by this authorKlara Komici
Department of Translational Medical Sciences, Federico II University, Naples, Italy
Search for more papers by this authorFranco Rengo
IRCCS, Scientific Institute of Telese Terme (BN), Salvatore Maugeri Foundation, Telese Terme, Italy
Search for more papers by this authorBruno Trimarco
Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy
Search for more papers by this authorNicola Ferrara
IRCCS, Scientific Institute of Telese Terme (BN), Salvatore Maugeri Foundation, Telese Terme, Italy
Department of Translational Medical Sciences, Federico II University, Naples, Italy
Search for more papers by this authorCorresponding Author
Dario Leosco
Department of Translational Medical Sciences, Federico II University, Naples, Italy
Correspondence to: Dario Leosco, Section of Geriatrics, Department of Translational Medical Sciences, Federico II University, Via Pansini 5, 80131 Naples, Italy. Tel./fax: +39-081-7463677; e-mail: [email protected]
Or
Pasquale Perrone-Filardi, Section of Cardiology, Department of Advanced Biomedical Sciences, Federico II University, Via Pansini 5, 80131 Naples, Italy. Tel./fax: +39-081-7462224; e-mail: [email protected]
Search for more papers by this authorCorresponding Author
Pasquale Perrone-Filardi
Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy
Correspondence to: Dario Leosco, Section of Geriatrics, Department of Translational Medical Sciences, Federico II University, Via Pansini 5, 80131 Naples, Italy. Tel./fax: +39-081-7463677; e-mail: [email protected]
Or
Pasquale Perrone-Filardi, Section of Cardiology, Department of Advanced Biomedical Sciences, Federico II University, Via Pansini 5, 80131 Naples, Italy. Tel./fax: +39-081-7462224; e-mail: [email protected]
Search for more papers by this authorGiuseppe Rengo
IRCCS, Scientific Institute of Telese Terme (BN), Salvatore Maugeri Foundation, Telese Terme, Italy
Search for more papers by this authorGennaro Pagano
Department of Medicine and Health Sciences, University of Molise, Campobasso, Italy
Department of Translational Medical Sciences, Federico II University, Naples, Italy
Search for more papers by this authorStefania Paolillo
Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy
Search for more papers by this authorClaudio de Lucia
Department of Translational Medical Sciences, Federico II University, Naples, Italy
Search for more papers by this authorGrazia D. Femminella
Department of Translational Medical Sciences, Federico II University, Naples, Italy
Search for more papers by this authorDaniela Liccardo
Department of Translational Medical Sciences, Federico II University, Naples, Italy
Search for more papers by this authorAlessandro Cannavo
Department of Translational Medical Sciences, Federico II University, Naples, Italy
Search for more papers by this authorRoberto Formisano
Department of Translational Medical Sciences, Federico II University, Naples, Italy
Search for more papers by this authorLaura Petraglia
Department of Translational Medical Sciences, Federico II University, Naples, Italy
Search for more papers by this authorKlara Komici
Department of Translational Medical Sciences, Federico II University, Naples, Italy
Search for more papers by this authorFranco Rengo
IRCCS, Scientific Institute of Telese Terme (BN), Salvatore Maugeri Foundation, Telese Terme, Italy
Search for more papers by this authorBruno Trimarco
Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy
Search for more papers by this authorNicola Ferrara
IRCCS, Scientific Institute of Telese Terme (BN), Salvatore Maugeri Foundation, Telese Terme, Italy
Department of Translational Medical Sciences, Federico II University, Naples, Italy
Search for more papers by this authorCorresponding Author
Dario Leosco
Department of Translational Medical Sciences, Federico II University, Naples, Italy
Correspondence to: Dario Leosco, Section of Geriatrics, Department of Translational Medical Sciences, Federico II University, Via Pansini 5, 80131 Naples, Italy. Tel./fax: +39-081-7463677; e-mail: [email protected]
Or
Pasquale Perrone-Filardi, Section of Cardiology, Department of Advanced Biomedical Sciences, Federico II University, Via Pansini 5, 80131 Naples, Italy. Tel./fax: +39-081-7462224; e-mail: [email protected]
Search for more papers by this authorCorresponding Author
Pasquale Perrone-Filardi
Department of Advanced Biomedical Sciences, Federico II University, Naples, Italy
Correspondence to: Dario Leosco, Section of Geriatrics, Department of Translational Medical Sciences, Federico II University, Via Pansini 5, 80131 Naples, Italy. Tel./fax: +39-081-7463677; e-mail: [email protected]
Or
Pasquale Perrone-Filardi, Section of Cardiology, Department of Advanced Biomedical Sciences, Federico II University, Via Pansini 5, 80131 Naples, Italy. Tel./fax: +39-081-7462224; e-mail: [email protected]
Search for more papers by this authorAbstract
Background
Diabetes mellitus (DM) is associated with impaired prognosis in patients with heart failure (HF), but pathogenic mechanisms are unclear. In the failing heart, elevated β-adrenergic receptor (β-AR) activation by catecholamines causes G-protein-coupled receptor kinase-2 (GRK2) upregulation which is responsible for β-AR signalling dysfunction. Importantly, GRK2 expression, measured in peripheral lymphocytes of HF patients, correlates with levels of this kinase in the failing myocardium reflecting the loss of hemodynamic function. Moreover, HF-related GRK2 protein overexpression promotes insulin resistance by interfering with insulin signalling. The aim of this study was to assess lymphocyte GRK2 protein levels in HF patients with and without DM.
Methods and materials
Patients with a diagnosis of HF were enrolled in the study. All subjects underwent a complete clinical examination (including NYHA functional class assessment and echocardiography) and blood draw for serum N-terminal pro-brain natriuretic peptide (NT-proBNP), lymphocyte GRK2 and plasma norepinephrine (NE) levels. Demographic data including age, sex, medications, cardiovascular risk factors and presence of comorbidities were also collected.
Results
Two hundred and sixty-eight patients with HF (left ventricular ejection fraction [LVEF] 30·6 ± 7·6%) with and without DM were enrolled. No differences between the two groups were found in terms of demography, HF aetiology, LVEF, NYHA class, NE and NT-proBNP. GRK2 was significantly higher in patients with DM compared to non-DM. At multivariate linear regression analysis, LVEF, NE, NT-proBNP and diabetes came out to be independent predictors of GRK2 levels in the overall study population.
Conclusion
In HF patients, DM is associated with significantly more elevated lymphocyte GRK2 protein levels, likely reflecting more compromised cardiac β-AR signalling/function, despite similar hemodynamic status and neuro-hormonal activation compared to patients without DM. These findings contribute to explain the negative prognostic impact of DM in patients with HF.
Supporting Information
| Filename | Description |
|---|---|
| eci12395-sup-0001-FigS1.tifimage/tif, 341.3 KB | Figure S1. Correlation between HbA1c and lymphocyte GRK2 protein levels in 60 HF patients with DM. |
| eci12395-sup-0002-FigS2.tifimage/tif, 390.3 KB | Figure S2. Correlation between DM duration and lymphocyte GRK2 protein levels in 60 HF patients with DM. |
| eci12395-sup-0003-TableS1.docWord document, 45.5 KB | Table S1. Characteristic of DM HF patients. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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