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Rengo, G., Pagano, G., Filardi, P.P., Femminella, G.D., Parisi, V., Cannavo, A., Liccardo, D., Komici, K., Gambino, G., D'Amico, M.L., De Lucia, C., Paolillo, S., Trimarco, B., Vitale, D.F., Ferrara, N., Koch, W.J., Leosco, D.
Prognostic value of lymphocyte G protein-coupled receptor kinase-2 protein levels in patients with heart failure
(2016) Circulation Research, 118 (7), pp. 1116-1124. 
https://www.scopus.com/inward/record.uri?eid=2-s2.0-84994571224&partnerID=40&md5=c040107e0a990576873a37b9e36f8191

DOI: 10.1161/CIRCRESAHA.115.308207
AFFILIATIONS: Division of Cardiology, Salvatore Maugeri Foundation, IRCCS, Scientific Institute of Telese Terme (BN), Italy; 
Division of Geriatrics, Department of Translational Medical Sciences, University of Naples Federico II, Via S. Pansini, 5, Naples, Italy; 
Division of Cardiology, Department of Advanced Biomedical Sciences, Federico II University of Naples, Naples, Italy; 
SDN Foundation IRCCS, Institute of Diagnostic and Nuclear Development, Naples, Italy; 
Department of Pharmacology, Center of Translational Medicine, Temple University School of Medicine, 3500 N Broad St., Philadelphia, PA, United States
ABSTRACT: Rationale: Sympathetic nervous system hyperactivity is associated with poor prognosis in patients with heart failure (HF), yet routine assessment of sympathetic nervous system activation is not recommended for clinical practice. Myocardial G protein-coupled receptor kinase-2 (GRK2) is upregulated in HF patients, causing dysfunctional β-adrenergic receptor signaling. Importantly, myocardial GRK2 levels correlate with levels found in peripheral lymphocytes of HF patients. Objective: The independent prognostic value of blood GRK2 measurements in HF patients has never been investigated; thus, the purpose of this study was to evaluate whether lymphocyte GRK2 levels predict clinical outcome in HF patients. Methods and Results: We prospectively studied 257 HF patients with mean left ventricular ejection fraction of 31.4±8.5%. At the time of enrollment, plasma norepinephrine, serum NT-proBNP, and lymphocyte GRK2 levels, as well as clinical and instrumental variables were measured. The prognostic value of GRK2 to predict cardiovascular (CV) death and all-cause mortality was assessed using the Cox proportional hazard model including demographic, clinical, instrumental, and laboratory data. Over a mean follow-up period of 37.5±20.2 months (range, 3-60 months), there were 102 CV deaths. Age, left ventricular ejection fraction, New York Heart Association class, chronic obstructive pulmonary disease, chronic kidney disease, N-terminal-pro brain natriuretic peptide, and lymphocyte GRK2 protein levels were independent predictors of CV mortality in HF patients. GRK2 levels showed an additional prognostic and clinical value over demographic and clinical variables. The independent prognostic value of lymphocyte GRK2 levels was also confirmed for all-cause mortality. Conclusions: Lymphocyte GRK2 protein levels can independently predict prognosis in patients with HF. © 2016 American Heart Association, Inc.
CORRESPONDENCE ADDRESS: Koch, W.J.; Department of Pharmacology, Center of Translational Medicine, Temple University School of Medicine, 3500 N Broad St., United States; email: walter.koch@temple.edu

Scopus news

Femminella, G.D., Leosco, D., Ferrara, N., Rengo, G.
Adrenergic drugs blockers or enhancers for cognitive decline? What to choose for Alzheimer’s disease patients?
(2016) CNS and Neurological Disorders - Drug Targets, 15 (6), pp. 665-671. 
https://www.scopus.com/inward/record.uri?eid=2-s2.0-84981517805&partnerID=40&md5=5d7501b75b13602b5449932d466a63ce

AFFILIATIONS: Division of Geriatrics, Department of Translational Medical Sciences, University of Naples Federico II, Naples, Italy; 
Salvatore Maugeri Foundation, IRCCS, Scientific Institute of Telese Terme, Telese Terme, BN, Italy
ABSTRACT: The adrenergic system has an important role in normal central nervous system function as well as in brain disease. The locus coeruleus, the main source of norepinephrine in brain, is involved in the regulation of learning and memory, reinforcement of sleep-wake cycle and synaptic plasticity. In Alzheimer’s disease, locus coeruleus degeneration is observed early in the course of the disease, years before the onset of clinical cognitive signs, with neurofibrillary detected at the stage of mild cognitive impairment, preceding amyloid deposition. Thus, in the last years, a great interest has grown in evaluating the possibility of central adrenergic system modulation as a therapeutic tool in Alzheimer’s disease. However, evidences do not show univocal results, with some studies suggesting that adrenergic stimulation might be beneficial in Alzheimer’s Disease and some others favoring adrenergic blockade. In this review, we summarize data from both hypothesis and describe the pathophysiological role of the adrenergic system in neurodegeneration. © 2016 Bentham Science Publishers.
CORRESPONDENCE ADDRESS: Rengo, G.; Department of Translational Medical Sciences, University of Naples Federico II, Via Sergio Pansini 5, Italy; email: giuseppe.rengo@unina.it
DOCUMENT TYPE: Article

SCOPUS news

Femminella, G.D.a , De Lucia, C.a , Parisi, V.a , Silvestri, C.a , Petraglia, L.a , Formisano, R.a , Allocca, E.a , Ratto, E.a , Komici, K.a , Zincarelli, C.b , Rengo, F.b , Ferrara, N.b , Leosco, D.b 

β-adrenergic receptor involvment in Alzheimer disease [Coinvolgimento del signaling β-adrenergico nella malattia di Alzheimer]

(2014) Giornale di Gerontologia, 62 (3), pp. 95-100. 
https://www.scopus.com/inward/record.uri?eid=2-s2.0-84969857880&partnerID=40&md5=22a8afe856f495525916a63d2f42dc2c

AFFILIATIONS: a. Dipartimento di Scienze Mediche Translazionali, Università di Napoli “Federico II”, Italy; 
b.Fondazione “Salvatore Maugeri”, IRCCS, Istituto Scientifico di Telese Terme (BN), Italy

ABSTRACT: Since 1907, when it was first described, Alzheimer’s disease (AD) has been one of the most studied diseases, in order to clarify its complex pathogenesis. Since AD will become increasingly widespread in the next decades, resulting in enormous health care costs. Since current treatments do not alter the course of the disease, acting temporarily on symptoms, it is essential to identify factors involved in the pathogenesis of disease. Among these, the β-adrenergic receptor (β-ARs) system might play a crucial role. The central noradrenergic system undergoes substantial changes in the course of AD and β-ARs have been implicated both in the formation of amyloid in brain and in amyloid-induced neurotoxicity. Furthermore, it has been shown that GRK2, a G protein-coupled receptor kinase which regulates receptor desensitization and downregolation, has been implicated in neuronal dysfunction caused by amyloid deposition. Finally, GRK2 levels in circulating lymphocytes, which correlate with cognitive impairment, may be used as a biomarker to monitor cognitive decline and response to therapy. © 2014, Pacini Editore S.p.A. All rights reserved.
AUTHOR KEYWORDS: Alzheimer;  Cognitive impairment;  Dementia;  β-adrenergic receptor;  β-amyloid
DOCUMENT TYPE: Review