European Journal of Clinical Investigation (Eur J Clin Investig )

Publisher: European Society for Clinical Investigation, Blackwell Publishing

Description

The Journal of the European Society for Clinical Investigation. The European Journal of Clinical Investigation publishes papers in the field of clinical investigation, provided they contribute to the advancement of knowledge in this field. The term 'clinical investigation' is interpreted widely and includes studies relevant to humans in health or disease, including such studies that may have taken place with animals.

Impact factor 3.37

  • 5-year impact
    3.05
  • Cited half-life
    8.00
  • Immediacy index
    0.70
  • Eigenfactor
    0.01
  • Article influence
    0.90
  • Website
    European Journal of Clinical Investigation website
  • Other titles
    European journal of clinical investigation (Online)
  • ISSN
    1365-2362
  • OCLC
    46653881
  • Material type
    Document, Periodical, Internet resource
  • Document type
    Internet Resource, Computer File, Journal / Magazine / Newspaper

Publisher details

Blackwell Publishing

  • Pre-print
    • Author can archive a pre-print version
  • Post-print
    • Author cannot archive a post-print version
  • Restrictions
    • Some journals impose embargoes typically of 6 or 12 months, occasionally of 24 months
    • no listing of affected journals available as yet
  • Conditions
    • See Wiley-Blackwell entry for articles after February 2007
    • Publisher's version/PDF cannot be used
    • On author's server, institutional server or subject-based server
    • Server must be non-commercial
    • Publisher copyright and source must be acknowledged with set statement ("The definitive version is available at www.blackwell-synergy.com")
    • Articles in some journals can be made Open Access on payment of additional charge
    • 'Blackwell Publishing' is an imprint of 'Wiley'
  • Classification
    ​ yellow

Publications in this journal

  • Ivonne Loeffler, Gunter Wolf
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    ABSTRACT: Renal hypoxia is known to play an important role in the pathophysiology of acute renal injury as well as in other chronic kidney diseases. The mediators of hypoxia are the transcription factors HIF (hypoxia-inducible factors), that are highly regulated. Under normoxic conditions constitutively expressed HIF-α subunits are hydroxylated by prolyl hydroxylases (PHD1, PHD2, and PHD3) and subsequently degraded by proteasomes. The MAPK organizer 1 (Morg1) has been identified to act as a scaffold protein of PHD3 and suppression of Morg1 leads to the stabilization of HIF-α, which forms in the absence of oxygen a heterodimer with HIF-β, translocates to the nucleus and promotes the transcription of HIF target genes. This review summarizes the current knowledge regardingthe role of hypoxia, HIF signalling, and Morg1 in acute and chronic renal injury. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 01/2015;
  • Vivian G. Ng, Carlos Mena, Cody Pietras, Alexandra J. Lansky
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    ABSTRACT: Despite advancements from balloon angioplasty to drug-eluting stents, primary patency rates after endovascular revascularization of peripheral artery disease have remained inferior compared to surgery. Endovascular revascularization has been limited by restenosis and mechanical stent failure. Thus, there is increased research into other non-stent based local drug delivery modalities, which can provide an active drug to inhibit restenosis focally and avoid the risk of systemic adverse effects. This can be accomplished by direct drug application to the vessel wall either mechanically or via a local drug infusion. Paclitaxel has several chemical properties, which make it an ideal drug candidate for these novel delivery techniques. This paper will summarize the unique properties of paclitaxel and studies on paclitaxel local delivery for the treatment of peripheral artery disease.This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 01/2015;
  • Kadri Haller-Kikkatalo, Katrin Pruul, Kalle Kisand, Virge Nemvalts, Koit Reimand, Raivo Uibo
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    ABSTRACT: A proportion of phenotypic type 2 diabetes (T2D) patients produce pancreatic autoantibodies and a majority of T2D patients develop serious life-disabling complications over time despite the implementation of adequate clinical interventions. This study determined whether the presence of pancreatic autoantibodies (GADA, IA-2A, anti-ZnT8, or ICA) were associated with serious complications or concomitant diseases of adult patients diagnosed with T2D (N=305). In the study population, 22.3% (N=68) of subjects were positive for at least 1 of the 4 of the markers associated with autoimmune diabetes (presence of pancreatic autoantibody - pAb), followed by GADA (14.1%, N=43), ICA (8.9%, N=27), anti-ZnT8 (5.6%, N=17), and IA-2A (2.0%, N=6). Logistic regression analysis adjusted for patient's age, gender and duration of T2D revealed that: (i) pAb was associated with higher prevalence of adiposity (odds ratio of adjusted regression model (adOR) 2.51, p=0.032); (ii) pAb, GADA, and anti-ZnT8 were associated with autoimmune thyroid disease (adORs 3.07, p=0.012; 6.29, p<0.001 and 3.52, p=0.052, respectively); (iii) pAb and GADA, in particular, were risk factors for neurological complications (adORs 2.10, p=0.036; 2.76, p=0.009, respectively) and polyneuropathy in particular (adORs 2.60, p=0.012; 3.10, p=0.007, respectively); and (iv) anti-ZnT8 was a risk factor for developing nephropathy (adOR 4.61, p=0.022). In addition, adiposity was associated with 5.3-year earlier onset of disease (adjusted linear regression model, p=0.006). These results suggest that GADA and anti-ZnT8 are associated with progression of serious T2D complications, including polyneuropathy and nephropathy. In addition, adiposity represents a significant risk for autoimmunity development in T2D patients. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 01/2015;
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    ABSTRACT: Methylation of DNA and modifications of histones have emerged as intricately involved in gene regulation since they crosstalk and respond in multiple ways to the activity of transcription factors. Measuring these epigenome components has become a powerful tool to identify regulatory principles and biomarkers that predict cellular state during development or disease. Here I will focus on DNA methylation as a reversible epigenetic modification of DNA that has been studied in great detail at the level of the genome. Recent advances in sequencing have identified unexpected dynamics of this modification, which are tightly linked to gene regulation. Understanding how DNA methylation patterns are read and how they contribute to regulation will be critical to interpret and utilize genomic maps of DNA methylation. Since these patterns are dynamic during cellular differentiation and perturbed in disease they present an opportunity to use DNA methylation as a biomarker.This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 01/2015;
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    ABSTRACT: Background The essential amino acid tryptophan is required for protein synthesis, formation of the neurotransmitter serotonin and may exert immunoregulatory functions. An accelerated tryptophan breakdown rate is associated with inflammation and immune activation.Materials and methodsSerum concentrations of free tryptophan, neopterin and high sensitivity C-reactive protein (hsCRP) were measured in 1196 patients with coronary artery disease (CAD) derived from the LUdwigshafen RIsk and Cardiovascular Health (LURIC) study.ResultsTryptophan concentrations did not differ between patients with (mean±SD: 40.1±9.8 μmol/L) or without (42.3±23.9 μmol/L; not significant, Welch's test) angiographic CAD but patients with CAD had higher neopterin (9.1±8.2 nmol/L) and hsCRP (9.3±18.5 mg/L) concentrations compared to patients without (neopterin: 7.6±4.7 nmol/L, hsCRP: 5.8±7.6 mg/L; both p<0.0001). There existed an inverse correlation between serum tryptophan and neopterin (Spearman's rank correlation: rs = -0.273) and hsCRP (rs = -0.163; both p <0.0001) concentrations. Median observation time was 10.5 years, 385 patients had died, including 244 patients due to cardiovascular and 132 due to non-cardiovascular causes. After adjustments for cardiovascular risk factors and other possible confounders, the hazard ratio (with 95% CI) in the first tryptophan quartile of the study population was 1.51 (1.19-1.90; p=0.0006) for total mortality, 1.41 (1.05-1.89; p=0.0224) for cardiovascular and 1.79 (1.20-2.67; p=0.0042) for non-cardiovascular mortality, respectively, thus indicating a significantly higher risk of death in patients with tryptophan concentrations <34 μmol/L.Conclusions Low serum tryptophan in CAD patients is associated with immune activation and indicates reduced life expectancy.This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 01/2015;
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    ABSTRACT: Coronary atherothrombosis due to atherosclerotic plaque rupture or erosion is frequently associated with acute coronary syndromes (ACS). Significant efforts have been made to elucidate the pathophysiological mechanisms underlying acute coronary events. This narrative review is based on the material searched for and obtained via PubMed up to August 2014. The search terms we used were: "Angiotensin, acute coronary syndromes, acute myocardial infarction" in combination with "Atherosclerosis, vulnerability, clinical trial, ACE inhibitors, inflammation". Among several regulatory components, the renin-angiotensin system (RAS) was shown as a key pathway modulating coronary atherosclerotic plaque vulnerability. Indeed, these molecules are involved in all stages of atherogenesis. Classically, the RAS is composed by a series of enzymatic reactions leading to the Angiotensin (Ang) II generation and activity. However, the knowledge of RAS has expanded and become more complex. The discovery of novel components and their functions have revealed additional pathways that contribute to or counter-balance the actions of Ang II. In this review, we discussed on recent findings concerning the role of different Angiotensin peptides in the pathophysiology of ACS and coronary atherothrombosis, exploring the link between these molecules and atherosclerotic plaque vulnerability. Treatments selectively targeting Angiotensins (including Mas and AT2 agonists, ACE2 recombinant, or Ang-(1-7) and alamandine in oral formulations) have been tested in animal studies or in small human subgroups, expanding the perspective in the ACS prevention. These novel strategies, especially in the counter-regulatory axis ACE2/Ang-(1-7)/Mas, might be promising to reduce plaque vulnerability and inflammation. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 01/2015;
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    ABSTRACT: Background Treatment of ST elevation myocardial infarction (STEMI) has improved enormously since the introduction of primary percutaneous coronary intervention (pPCI). It remains unclear whether differences in survival between women and men treated with pPCI exist and if these potential differences can be explained by gender or by differences in baseline- or procedural characteristics. Therefore we systematically reviewed the available evidence.Materials and methodsOn 10-05-2013 Pubmed, Embase and Cochrane were searched for studies comprising original data on STEMI patients treated with pPCI. A separate gender analysis including > 100 women was a requirement. Data were extracted and pooled whenever possible.Results21 studies were included from 2001 to 2013 comprising 47.439 men and 16.927 women. Women were older, had more diabetes (women 24%, men 15%) and hypertension (women 58%, men 45%) and were less current smokers (women 30%, men 54%). The procedural characteristics were comparable except for a longer symptom-to-balloon-time (women 266 min, men 240 min) and less use of GP-IIb/IIIa-inhibitors in women (women 51%, men 57%). Crude short- and long-term mortality was higher in women. Although we could not pool adjusted mortality proportions due to heterogeneity, generally the difference in mortality disappeared after adjustment for baseline- and procedural characteristics.In conclusionMortality is higher in women with STEMI and can be explained by their unfavourable risk profile and longer symptom-to-balloon time.This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 01/2015;
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    ABSTRACT: Background Tissue-specific dipeptidyl-peptidase 4 (DPP4) dysregulation has been described in adults with diabetes mellitus. The DPP4 -incretin system have not been studied in fetal life. In the present study DPP4 activity and GLP-1 levels were assessed in cord blood of neonates born to women with gestational diabetes mellitus (GDM) and non-diabetic controls.Material and methodsThis study has been conducted in two Hungarian and one Austrian center. Patients: 568 pregnant women were enrolled to the study after their OGTT between the 24-28th gestational week. Cord blood samplings with DPP4 activity and GLP-1 level measurements were possible in 270 (DPP4: 159 control, 111 GDM) and 112 (GLP-1: 72 control, 40 GDM) cases. OGTT (24-28th gestational week) and cord blood sampling at delivery. Cord serum DPP4 activity was determined in a continuous monitoring microplate-based kinetic assay, cord plasma GLP-1 was measured using a fluorescence ELISA method.ResultsCord serum DPP4 activity was lower in GDM [Mean (95%CI): 28.07U/L (26.32-29.82 U/L)] than in controls [31.67U/L (29.93-33.29 U/L), MWU p=0.0015]. Cord plasma active GLP-1 levels were close to the lower detection limit and were not altered in GDM (Control: Mean=3.43pmol/L, 95%CI:3.04-3.82pmol/L, GDM: Mean= 3.61pmol/L, 95%CI:2.96-4.28pmol/L – MWU-test p=0.6).Conclusions Decreased cord serum DPP4 activity in gestational diabetes mellitus might be the result of an adaptive fetal response or an early dysregulation in the entero-insular axis with consequences beyond the incretin system. Cord plasma GLP-1 levels may reflect the missing oral intake with a limited glucose sensing of L-Cells via the circulation in fetal life.This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 01/2015;
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    ABSTRACT: Background Regular gallbladder contraction reduces bile stasis and prevents gallstone formation. Intraduodenal administration of exogenous pancreatic secretory trypsin inhibitor (PSTI-I, also known as monitor peptide) causes cholecystokinin (CCK) secretion.DesignWe proposed that stimulation of CCK release by PSTI would produce gallbladder contraction and prevent gallstones in mice fed a lithogenic diet. Therefore, we tested the effect of overexpression of rat PSTI-I in pancreatic acinar cells on plasma CCK levels and gallbladder function in a transgenic mouse line (TgN[Psti1]; known hereafter as PSTI-I tg).ResultsImportantly, PSTI tg mice had elevated fasting and fed plasma CCK levels compared to wild-type (WT) mice. Only mice fed the lithogenic diet developed gallstones. Both fasting and stimulated plasma CCK levels were substantially reduced in both WT and PSTI-I tg mice on the lithogenic diet. Moreover, despite higher CCK levels PSTI-I tg animals developed more gallstones than WT animals.Conclusions Together with the previously observed decrease in CCK-stimulated gallbladder emptying in mice fed a lithogenic diet, our findings suggest that a lithogenic diet causes gallstone formation by impaired CCK secretion in addition to reduced gallbladder sensitivity to CCK.This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 01/2015;
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    ABSTRACT: The adaptor protein p66Shc links membrane receptors to intracellular signalling pathways and has the potential to respond to energy status changes and regulate mitogenic signalling. Initially reported to mediate growth signals in normal and cancer cells, p66Shc has also been recognized as a pro-apoptotic protein involved in the cellular response to oxidative stress. Moreover, it is a key element in processes such as cancer cell proliferation, tumor progression, metastasis and metabolic reprogramming. Recent findings on the role of p66Shc in the above-mentioned processes have been obtained through the use of various tumor cell types, including prostate, breast, ovarian, lung, colon, skin and thyroid cancer cells. Interestingly, the impact of p66Shc on the proliferation rate was mainly observed in prostate tumors, while its impact on metastasis was mainly found in breast cancers. In this review, we summarize the current knowledge about the possible roles of p66Shc in different cancers.
    European Journal of Clinical Investigation 01/2015; 45(s1).
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    ABSTRACT: Background Epigenetic control of gene expression is mediated by cytosine methylation/demethylation and histone modifications including methylation, acetylation and glycosylation. The epigenetic programme is corrupted in cancer cells to maintain a pattern of gene expression that leads to their de-differentiated, rapidly proliferating phenotype. Enzymes responsible for modifying histones and cytosine are sensitive to the cellular metabolite pool and can be activated by an increase in their substrates or inhibited by an increase in their products or competitors for substrate binding.Methods This review is based on publications identified on PubMed using a literature search of cytosine methylation, histone methylation, acetylation and glycosylation.ResultsIn cancer, changes in glycolytic enzymes lead to increased production of serine, increasing the pool of S-adenosylmethionine (the major methyl donor for methylation reactions) and UDP-N-acetylglucosamine (a substrate for O-linked glycosylation of histones and cytosine methyltransferases). Mutations in tricarboxylic acid cycle enzymes lead to accumulation of fumarate, succinate and hydroxyglutarate, all of which inhibit demethylation of cytosine and histones. In contrast, proline catabolism produces α-ketoglutarate and reactive oxygen, both of which promote the activity of enzymes that remove methyl groups from cytosine and histones, and the key enzyme in proline catabolism acts as a tumour suppressor.Conclusions Our emerging understanding of how the epigenetic profiles are metabolically reprogrammed in cancer cells will lead to novel diagnostic and therapeutic targets for treatment of patients.
    European Journal of Clinical Investigation 01/2015; 45(s1).
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    ABSTRACT: Background Bisphenol A (BPA) is one of the most widely produced chemicals worldwide and is often used in the production of food and beverage containers. As a result of BPA contact with food, drink and toiletries, its ingestion and absorption by humans has been growing. The industrialization and modern lifestyles brought a constant exposure to several health-disturbing compounds and ushered a new era of chronic diseases. The endocrine disruptor potential of BPA is well known, but the research around its epigenotoxic effects raised further concerns whether chronic exposure to BPA can contribute to chronic human illness, including cancer in hormone-sensitive organs.Materials and methodsFocusing on computerized databases, we reviewed original and review articles which elucidate and link some of the information already available about BPA and related epigenetic alterations.ResultsA number of studies indicate that short-term administration of low or high-doses of BPA may be associated with an increased risk of epigenetic modifications, increasing the risk for carcinogenesis. However, it is clear that more studies considering real daily exposures are essential to define a real tolerable daily intake and to tighten\xA0up\xA0manufactory regulations.Conclusion In this review, we highlight some evidences suggesting a relationship between BPA exposure, genotoxic activity and epigenetic modifications, which may prime for carcinogenesis.
    European Journal of Clinical Investigation 01/2015; 45(s1).
  • Christiana A. Demetriou, Karin Veldhoven, Caroline Relton, Silvia Stringhini, Kyriacos Kyriacou, Paolo Vineis
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    ABSTRACT: Background Following wider acceptance of “the thrifty phenotype” hypothesis and the convincing evidence that early life exposures can influence adult health even decades after the exposure, much interest has been placed on the mechanisms through which early life exposures become biologically embedded.Methods In this review, we summarize the current literature regarding biological embedding of early life experiences. To this end we conducted a literature search to identify studies investigating early life exposures in relation to DNA methylation changes. In addition, we summarize the challenges faced in investigations of epigenetic effects, stemming from the peculiarities of this emergent and complex field. A proper systematic review and meta-analyses were not feasible given the nature of the evidence.ResultsWe identified 7 studies on early life socioeconomic circumstances, 10 studies on childhood obesity, and 6 studies on early life nutrition all relating to DNA methylation changes that met the stipulated inclusion criteria. The pool of evidence gathered, albeit small, favours a role of epigenetics and DNA methylation in biological embedding, but replication of findings, multiple comparison corrections, publication bias, and causality are concerns remaining to be addressed in future investigations.Conclusions Based on these results, we hypothesize that epigenetics, in particular DNA methylation, is a plausible mechanism through which early life exposures are biologically embedded. This review describes the current status of the field and acts as a stepping stone for future, better designed investigations on how early life exposures might become biologically embedded through epigenetic effects.This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 01/2015;
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    ABSTRACT: Background In rodents, it has previously been shown that Necrostatin-1 (Nec-1) inhibits RIP1, a central regulator of programmed necrosis, thereby decreasing cell death and reducing infarct size after ischemia/reperfusion (I/R) injury. To address unanswered questions on feasibility and efficacy of Nec-1 in a large animal model, we assessed the effects of Nec-1 in a porcine I/R model, relevant to human disease.Materials and Methods In Dalland landrace pigs (69±3kg), I/R injury was induced by a 75-min surgical ligation of the left circumflex coronary artery (LCx). Ten minutes prior to reperfusion, pigs were randomly allocated to different Nec-1 doses (1.0mg/kg or 3.3mg/kg) or vehicle treatment (CTRL). Functional endpoints and immunohistological analyses were performed 24 hours after reperfusion.ResultsNec-1 3.3mg/kg significantly reduced infarct size (n=6; 24.4±15.6%) compared to Nec-1 1.0 mg/kg (n=5; 54.8±16.9%) or CTRLs (n=6; 62.1±26.6%; P=0.016). In line, LVEF was significantly higher in Nec-1 3.3mg/kg, compared to Nec-1 1.0mg/kg or CTRL treated animals (50.0±12.0% vs 32.5±12.9% vs 31.9±6.6% respectively, P=0.015). Hemodynamically, a preserved contractility was observed (end systolic volume at 100 mmHg (ESV100)) at 24-hours follow up (87.6±17.3 ml vs. 74.5±41.1 ml vs. 56.8±11.8 ml, respectively; P=0.032), reflecting improved cardiac function.Conclusions In the pig model of I/R injury, intravenous administration of Nec-1 prior to reperfusion was an effective and above all practical therapeutic strategy that significantly reduced infarct size and preserved left ventricular function. These data highlight the potential of cardioprotection as a promising adjuvant therapy in the setting of early reperfusion following I/R injury.This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 12/2014;
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    ABSTRACT: Background Post-operative atrial fibrillation (POAF) is a common complication after cardiac surgery and predicts increased morbidity and mortality. Identification of patients at high risk of POAF with the help of circulating biomarkers may enable early preventive treatment but data are limited, especially in contemporary surgical patients.Methods Plasma concentrations of N-terminal pro B-type natriuretic peptide (NT-proBNP) and high sensitivity cardiac troponin T (hs-cTnT) were measured at enrollment, on the morning of cardiac surgery, at end-surgery, and 2 days post-surgery in 562 patients undergoing cardiac surgery, randomized to perioperative supplementation with oral fish oil or placebo in the Omega-3 Fatty Acids for Prevention of Post-Operative Atrial Fibrillation trial (OPERA). The primary endpoint was incident POAF lasting ≥ 30seconds, centrally adjudicated and confirmed electrocardiographically.ResultsHigher levels of NT-proBNP and hs-cTnT before surgery were associated with older age, renal or cardiac dysfunction and EuroSCORE. NT-proBNP peaked on post-operative day 2 (2172 [1238-3758] ng/L, median [Q1-Q3]), while hs-cTnT peaked at the end of surgery (373 [188-660] ng/L). Fish oil supplementation did not alter the time course of the cardiac biomarkers (p>0.05). Concentrations of NT-proBNP or hs-cTnT, on the morning of surgery, or changes in their level between morning of surgery and post-surgery, were not significantly associated with POAF after adjustment for clinical and surgical characteristics.Conclusion Among patients undergoing cardiac surgery, NT-proBNP and hs-cTnT are related to clinical and surgical characteristics, have different perioperative time courses but are not independently associated with risk of POAF.This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 12/2014;
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    ABSTRACT: 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 (βAR) activation by catecholamines causes G-protein coupled receptor kinase-2 (GRK2) up-regulation which is responsible for βAR signaling 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 signaling. The aim of the present study was to assess lymphocyte GRK2 protein levels in HF patients with and without DM.Methods and materialsPatients 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.Results268 patients with HF (left ventricular ejection fraction [LVEF] 30.6±7.6%) with and without DM were enrolled. No differences between the 2 groups were found in terms of demography, HF etiology, LVEF, NYHA class, NE and NT-proBNP. GRK2 was significantly higher in DM patients 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 signaling/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 pts with HF.This article is protected by copyright. All rights reserved.
    European Journal of Clinical Investigation 12/2014;