M. Zeller

Unité Inserm U1077, Caen, Lower Normandy, France

Are you M. Zeller?

Claim your profile

Publications (239)803.9 Total impact

  • Luc Rochette · Marianne Zeller · Yves Cottin · Catherine Vergely ·
    [Show abstract] [Hide abstract]
    ABSTRACT: Members of the TGF-β superfamily transduce their signals through type I and II receptor serine/threonine kinases. The regulation of members of the TGF-β family is known to be complex, because many proteins able to bind the ligands and inhibit their activities have been identified. Growth and differentiation factor 11 (Gdf11) as activins belong to the TGF-β family. GDF11, like other members of the TGF-β superfamily, is produced from precursor proteins by proteolytic processing. The binding of activins to activin type IIA (ActRIIA) or type IIB (ActRIIB) receptors induces the recruitment and phosphorylation of an activin type I receptor which then phosphorylates the Smad2 and Smad3 intracellular signaling proteins. GDF11 signal through the ActRIIB pathway. Recent studies have reported that GDF11-ActRIIB-Smad2/3-dependent signaling is a key regulatory mechanism in proliferating erythroid precursors as it controls their late-stage maturation. The administration of GDF11 is effective in experimental cardiac hypertrophy, and the identification of GDF11 as a "rejuvenating factor" opens up perspectives for the treatment of age-related cardiac dysfunction. Recent studies of the heart indicate that exposure to young blood reverses age-related impairments. GDF11 could be one of the circulating molecules that influence the aging of different tissues. Is GDF11 an "elixir of youth"?
    Pharmacology [?] Therapeutics 11/2015; DOI:10.1016/j.pharmthera.2015.10.006 · 9.72 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Atrial fibrillation (AF), whether silent or symptomatic, is a frequent and severe complication of acute myocardial infarction (AMI). Asymmetric dimethylarginine (ADMA), an endogenous eNOS inhibitor, is a risk factor for endothelial dysfunction. We addressed the relationship between ADMA plasma levels and AF occurrence in AMI. 273 patients hospitalized for AMI were included. Continuous electrocardiographic monitoring (CEM) ≥48 hours was recorded and ADMA was measured by High Performance Liquid Chromatography on admission blood sample. The incidence of silent and symptomatic AF was 39(14%) and 29 (11%), respectively. AF patients were markedly older than patients without AF (≈ 20 y). There was a trend towards higher ADMA levels in patients with symptomatic AF than in patients with silent AF or no AF (0.53 vs 0.49 and 0.49 μmol/L, respectively, p = 0.18,). After matching on age, we found that patients with symptomatic AF had a higher heart rate on admission and a higher rate of patients with LV dysfunction (28% vs. 3%, p = 0.025). Patients who developed symptomatic AF had a higher ADMA level than patients without AF (0.53 vs. 0.43 μmol/L; p = 0.001). Multivariate logistic regression analysis to estimate symptomatic AF occurrence showed that ADMA was independently associated with symptomatic AF (OR: 2.46 [1.21-5.00], p = 0.013) beyond history of AF, LVEF<40% and elevated HR. We show that high ADMA level is associated with the occurrence of AF. Although no causative role can be concluded from our observational study, our work further supports the hypothesis that endothelial dysfunction is involved in the pathogenesis of AF in AMI.
    PLoS ONE 07/2015; 10(7):e0131439. DOI:10.1371/journal.pone.0131439 · 3.23 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In secondary prevention (SP) of coronary artery disease (CAD), in particular after an acute myocardial infarction (MI), a better knowledge and self-management by the patient may have various supports. The Log book (LB) for CAD patients in Côte d'Or, was created in 2010 by a multidisciplinary team of healthcare professionals of Côte d'Or, from a regional care network. This pilot study evaluated LB as novel support for SP after acute MI. A prospective study on 183 patients hospitalised for an acute MI in the region of Côte d'Or from 1st May to 30th October 2010. Patients were randomized in 91 patients who received an LB at the time of their hospitalisation (LB+ group), and 92 patients who were not given an LB (LB- group). The follow up (FU) was performed at 4 months and 1 year. Baseline characteristics were similar in the 2 groups, except for smoking, which was more frequent in the LB-group than in the LB+ group. At FU, LB was usually well accepted by both patients and their general practitioners (GP). At 4 months FU, the patients LB+ were more prone to see their general practitioners than patients LB- (100% vs 85% in the LB- group, P=0.007). Moreover, in LB+ group, there was a trend towards a more frequent physical activity, including exercise bike (P=0.009) and an increase in HDL-cholesterol (HDL-c) (P=0.165). At 1 year FU, body mass index from LB+ was more reduced than in patients LB- (P=0.029). Finally, there was a trend towards lower morbi-mortality (hospitalisation for cardiovascular cause or death) in the LB+ group than in the LB- group (11 vs 22%, P=0.083). This pilot study showed the feasibility of LB as a support for SP and its interest in post MI management in a local care network setting. In addition, our study provides encouraging data on the potential benefits of this pioneer tool for SP. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
    La Presse Médicale 07/2015; 44(9). DOI:10.1016/j.lpm.2014.11.020 · 1.08 Impact Factor
  • Source

  • [Show abstract] [Hide abstract]
    ABSTRACT: Contrast-induced nephropathy (CIN) after percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) is frequent and associated with long-term renal impairment and mortality. Early markers of CIN are needed to improve risk stratification. We aimed to assess whether N-terminal fragment of pro B-type natriuretic peptide (Nt-proBNP) could be associated with CIN. From the French regional RICO survey, all the consecutive patients who underwent primary PCI for STEMI, from January 1, 2001, to December 3, 2013, were included. Nt-proBNP circulating levels were assessed on admission. CIN was defined as an increase in serum creatinine >26.5 μmol/L or >50% within 48 to 72 hours after PCI (KDIGO criteria). Of the 1,243 patients included, CIN occurred in 130 patients (10.4%). Nt-proBNP levels were 5 times greater in patients who developed CIN than without CIN (1,275 [435 to 4,022] vs 247 [79 to 986] pg/mL, p <0.001). Hospital mortality rate was markedly higher in patients with CIN (6.9% vs 1.1%, p <0.001). Nt-proBNP levels were univariate predictors for CIN as were age, hypertension, diabetes, smoking, previous stroke, heart rate, impaired left ventricular ejection fraction C-reactive protein, history of renal failure, anemia, and estimated glomerular filtration rate <30 ml/min/1.73 m(2) at baseline. Nt-proBNP levels remained strongly associated with the occurrence of CIN even after adjustment for risk factors, treatments, clinical and biological variables (odds ratio 1.99, 95% confidence interval 1.49 to 2.66). Net reclassification improvement was achieved by the addition of Nt-proBNP to the risk model (p = 0.003). In conclusion, from this large contemporary prospective study in nonselected population, our work suggests that Nt-proBNP levels at admission could help to identify patients at risk of CIN beyond traditional risk factors. Copyright © 2015 Elsevier Inc. All rights reserved.
    The American journal of cardiology 06/2015; 116(6). DOI:10.1016/j.amjcard.2015.06.007 · 3.28 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Silent atrial fibrillation (AF), assessed by continuous ECG monitoring (CEM), has recently been shown to be common in acute myocardial infarction (AMI), and associated with higher hospital mortality. However, the long-term prognosis is still unknown. We aimed to assess 1-year prognosis in patients experiencing silent AF in AMI. All consecutive patients with AMI who were prospectively analysed by CEM during the first 48 h after admission and who survived at hospital discharge were included. Silent AF was defined as asymptomatic episodes lasting at least 30 s. Patients were followed up at 1 year for cardiovascular (CV) outcomes. Among the 737 patients analysed, 106 (14%) developed silent AF and 32 (4%) symptomatic AF. Compared with the no-AF group, patients with silent AF were markedly older (79 vs 62 years, p<0.001), more frequently hypertensive (71% vs 49%, p<0.001) and less likely to be smokers (23% vs 37%, p<0.001). Also, they were more likely to have impaired LVEF (50% vs 55%, p<0.001). Risk factors in patients with silent AF were similar to those in patients with symptomatic AF. However, a history of stroke or AF was less frequent in silent AF than in symptomatic-AF patients (10% vs 25% and 10% vs 38%, respectively). At 1 year, CV events including hospitalisation for heart failure (HF) and CV mortality were markedly higher in silent-AF patients than in no-AF patients (6.6% vs 1.3% and 5.7% vs 2.0%, p<0.001, respectively). Our large prospective study showed for the first time that silent AF is associated with worse 1-year prognosis after AMI. Systematic screening and specific management should be investigated in order to improve outcomes of patients after AMI. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    Heart (British Cardiac Society) 04/2015; 101(11). DOI:10.1136/heartjnl-2014-307253 · 5.60 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Anticancer drugs continue to cause significant reductions in left ventricular ejection fraction resulting in congestive heart failure. The best-known cardiotoxic agents are anthracyclines (ANTHs) such as doxorubicin (DOX). For several decades cardiotoxicity was almost exclusively associated with ANTHs, for which cumulative dose-related cardiac damage was the use-limiting step. Human epidermal growth factor (EGF) receptor 2 (HER2; ErbB2) has been identified as an important target for breast cancer. Trastuzumab (TRZ), a humanized anti-HER2 monoclonal antibody, is currently recommended as first-line treatment for patients with metastatic HER2(+) tumors. The use of TRZ may be limited by the development of drug intolerance, such as cardiac dysfunction. Cardiotoxicity has been attributed to free-iron-based, radical-induced oxidative stress. Many approaches have been promoted to minimize these serious side effects, but they are still clinically problematic. A new approach to personalized medicine for cancer that involves molecular screening for clinically relevant genomic alterations and genotype-targeted treatments is emerging. Copyright © 2015. Published by Elsevier Ltd.
    Trends in Pharmacological Sciences 04/2015; 36(6). DOI:10.1016/j.tips.2015.03.005 · 11.54 Impact Factor

  • Revue Neurologique 04/2015; 171:A32. DOI:10.1016/j.neurol.2015.01.066 · 0.66 Impact Factor

  • Archives of Cardiovascular Diseases Supplements 01/2015; 7(1). DOI:10.1016/S1878-6480(15)71488-6

  • Archives of Cardiovascular Diseases Supplements 01/2015; 7(1). DOI:10.1016/S1878-6480(15)71493-X

  • Archives of Cardiovascular Diseases Supplements 01/2015; 7(1). DOI:10.1016/S1878-6480(15)71492-8

  • Archives of Cardiovascular Diseases Supplements 01/2015; 7(1). DOI:10.1016/S1878-6480(15)71530-2
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective: Takotsubo cardiomyopathy (TCM) is characterized by transient apical ventricular dysfunction typically induced by acute stress. Acute cerebral events including ischemic stroke (IS) or epileptic events (EEs) may be associated with massive catecholamine release. We aimed to identify the characteristics and outcomes of patients who experienced the Takotsubo syndrome complicated by IS or EE. Methods: Between 2008 and 2013, 87 patients were admitted to our intensive care unit for TCM. Of these, 6 had previously experienced acute cerebral symptoms within 2 days of experiencing either IS or EE. Takotsubo syndrome was diagnosed on cardiac MRI, echocardiography, electrocardiography (ECG), biology and coronary angiography data. Results: Five women and 1 man were included in the study. The mean age was 63.7 ± 20.1 years (range 44-84). Four of them (67%) initially presented an acute IS and 2 (33%) had EE. The suspected brain injury was found in the insular cortex for 4 patients and the posterior fossa for 2 patients. Hemiparesis, aphasia and cerebellar symptoms were the main neurological signs. Abnormal ECG findings including ST-segment elevation (33%) or T-wave inversion (50%) developed between a few hours and 48 h after the onset of the IS or EE. Peak troponin was 1.8 (0.79-14.11) µg/l. A transient reduction in the left ventricular ejection fraction (46 ± 12%) with apical hypokinesis was found using echocardiography. Two (33%) patients went on to develop acute heart failure. Coronary angiography confirmed the lack of significant coronary stenosis for all 6 patients. Conclusion: TCM can develop within the first few days after an acute cerebral event. It occurs predominantly in women with insular or posterior fossa lesions and is possibly induced by vegetative reactions.
    Archives of Cardiovascular Diseases Supplements 01/2015; 7(1):110. DOI:10.1016/S1878-6480(15)71802-1

  • Archives of Cardiovascular Diseases Supplements 01/2015; 7(1). DOI:10.1016/S1878-6480(15)71512-0

  • Archives of Cardiovascular Diseases Supplements 01/2015; 7(1). DOI:10.1016/S1878-6480(15)71508-9
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Myocardial infarction (MI) induces a sterile inflammatory response that contributes to adverse cardiac remodeling. The initiating mechanisms of this response remain incompletely defined. We found that necrotic cardiomyocytes released a heat-labile proinflammatory signal activating MAPKs and NF-κB in cardiac fibroblasts, with secondary production of cytokines. This response was abolished in Myd88(-/-) fibroblasts but was unaffected in nlrp3-deficient fibroblasts. Despite MyD88 dependency, the response was TLR independent, as explored in TLR reporter cells, pointing to a contribution of the IL-1 pathway. Indeed, necrotic cardiomyocytes released IL-1α, but not IL-1β, and the immune activation of cardiac fibroblasts was abrogated by an IL-1R antagonist and an IL-1α-blocking Ab. Moreover, immune responses triggered by necrotic Il1a(-/-) cardiomyocytes were markedly reduced. In vivo, mice exposed to MI released IL-1α in the plasma, and postischemic inflammation was attenuated in Il1a(-/-) mice. Thus, our findings identify IL-1α as a crucial early danger signal triggering post-MI inflammation. Copyright © 2014 by The American Association of Immunologists, Inc.
    The Journal of Immunology 12/2014; DOI:10.4049/jimmunol.1401948 · 4.92 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A number of liquid argon time projection chambers (LAr TPCs) are being built or are proposed for neutrino experiments on long- and short baseline beams. For these detectors, a distortion in the drift field due to geometrical or physics reasons can affect the reconstruction of the events. Depending on the TPC geometry and electric drift field intensity, this distortion could be of the same magnitude as the drift field itself. Recently, we presented a method to calibrate the drift field and correct for these possible distortions. While straight cosmic ray muon tracks could be used for calibration, multiple coulomb scattering and momentum uncertainties allow only a limited resolution. A UV laser instead can create straight ionization tracks in liquid argon, and allows one to map the drift field along different paths in the TPC inner volume. Here we present a UV laser feed-through design with a steerable UV mirror immersed in liquid argon that can point the laser beam at many locations through the TPC. The straight ionization paths are sensitive to drift field distortions, a fit of these distortion to the linear optical path allows to extract the drift field, by using these laser tracks along the whole TPC volume one can obtain a 3D drift field map. The UV laser feed-through assembly is a prototype of the system that will be used for the MicroBooNE experiment at the Fermi National Accelerator Laboratory (FNAL).
    Journal of Instrumentation 11/2014; 9(11):T11007. DOI:10.1088/1748-0221/9/11/T11007 · 1.40 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Smokeless tobacco (snuff) is a finely ground or shredded tobacco that is sniffed through the nose or placed between the cheek and gum. Chewing tobacco is used by putting a wad of tobacco inside the cheek. Smokeless tobacco is widely used by young athletes to enhance performance because nicotine improves some aspects of physiology. However, smokeless tobacco has harmful health effects, including cardiovascular disorders, linked to nicotine physiological effects, mainly through catecholamine release. Nicotine decreases heart rate variability and the ventricular fibrillation threshold, and promotes the occurrence of various arrhythmias; it also impairs endothelial-dependent vasodilation and could therefore promote premature atherogenesis. At rest, heart rate, blood pressure, inotropism, cardiac output and myocardial oxygen consumption are increased by nicotine, leading to an imbalance between myocardial oxygen demand and supply. The same occurs at submaximal levels of exercise. These increases are accompanied by a rise in systemic resistances. At maximal exercise, heart rate, cardiac output and maximal oxygen uptake (V˙O2max) are unaffected by nicotine. Because endothelial dysfunction is promoted by nicotine, paradoxical coronary vasoconstriction may occur during exercise and recovery. Nicotine induces a decrease in muscular strength and impairs anaerobic performance. However, nicotine is used in sports as it diminishes anxiety, enhances concentration and agility, improves aerobic performance and favours weight control. Importantly, smokeless tobacco, similar to cigarette smoking, leads to nicotine dependence through dopaminergic pathways. Smokeless tobacco has harmful cardiovascular effects and is addictive: it fulfils all the criteria for inclusion in the World Anti-Doping Agency prohibited list as a doping product. Smokeless tobacco use in sporting activities must be discouraged. Copyright © 2014 Elsevier Masson SAS. All rights reserved.
    Archives of Cardiovascular Diseases 11/2014; 108(1). DOI:10.1016/j.acvd.2014.10.003 · 1.84 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The maintenance of stable extracellular and intracellular iron concentrations requires the coordinated regulation of iron transport into plasma. Iron is a fundamental cofactor for several enzymes involved in oxidation–reduction reactions. The redox ability of iron can lead to the production of oxygen free radicals, which can damage various cellular components. Therefore, the appropriate regulation of systemic iron homeostasis is decisive in vital processes. Hepcidin has emerged as the central regulatory molecule of systemic iron homeostasis. It is synthesized in hepatocytes and in other cells and released into the circulation. It inhibits the release of iron from enterocytes of the duodenum and from macrophages by binding to the iron exporter protein, ferroportin (FPN). FPN is a transmembrane protein responsible for iron export from cells into the plasma. Hepcidin is internalized with FPN and both are degraded in lysosomes. The hepcidin-FPN axis is the principal regulator of extracellular iron homeostasis in health and disease. Its manipulation via agonists and antagonists is an attractive and novel therapeutic strategy. Hepcidin agonists include compounds that mimic the activity of hepcidin and agents that increase the production of hepcidin by targeting hepcidin-regulatory molecules. The inhibition of hepcidin could be a potentially attractive therapeutic strategy in patients suffering from anaemia or chronic inflammation. In this review, we will summarize the role of hepcidin in iron homeostasis and its contribution to the pathophysiology of inflammation and iron disorders. We will examine emerging new strategies that modulate hepcidin metabolism.
    Pharmacology [?] Therapeutics 09/2014; 146. DOI:10.1016/j.pharmthera.2014.09.004 · 9.72 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: ARGONTUBE is a liquid argon time projection chamber (TPC) with an electron drift length of up to 5 m equipped with cryogenic charge-sensitive preamplifiers. In this work, we present results on its performance including a comparison of the new cryogenic charge-sensitive preamplifiers with the previously used room-temperature-operated charge preamplifiers.
    Journal of Instrumentation 08/2014; 9(11). DOI:10.1088/1748-0221/9/11/P11022 · 1.40 Impact Factor

Publication Stats

6k Citations
803.90 Total Impact Points


  • 2015
    • Unité Inserm U1077
      Caen, Lower Normandy, France
  • 2014-2015
    • French Institute of Health and Medical Research
      Lutetia Parisorum, Île-de-France, France
    • University of Burgundy
      Dijon, Bourgogne, France
  • 2008-2013
    • Universität Bern
      • Laboratory for High Energy Physics
      Berna, Bern, Switzerland
  • 2010-2012
    • University of Freiburg
      • Faculty of Mathematics and Physics
      Freiburg, Lower Saxony, Germany
  • 1986-2006
    • Yale University
      • Department of Physics
      New Haven, Connecticut, United States
  • 2004
    • Centre Hospitalier Universitaire de Dijon
      Dijon, Bourgogne, France
  • 2001
    • University of Zurich
      Zürich, Zurich, Switzerland
  • 1992
    • University of Washington Seattle
      Seattle, Washington, United States
  • 1983-1985
    • University of California, Berkeley
      • Lawrence Berkeley Laboratory
      Berkeley, California, United States
  • 1978
    • Bielefeld University
      • Faculty of Physics
      Bielefeld, North Rhine-Westphalia, Germany