Introduction

Si le xixe siècle a vu naître et se multiplier les grandes collectes de contes européens, dans le sillage des Contes pour les enfants et la maison des frères Grimm, dont la première édition (décembre 1812), fêtait son bicentenaire en 2012, les adaptations et transpositions de ces récits populaires dans d’autres genres ne se sont pas fait attendre très longtemps. Dès les années 1830, Pouchkine reprenait non seulement le motif central, mais aussi toute la trame narrative du « Conte du pêcheur e..

Expression and implication of clusterin in left ventricular remodeling after myocardial infarction

International audienceBACKGROUND: Left ventricular remodeling (LVR) after myocardial infarction is associated with an increased risk of heart failure and death. In spite of a modern therapeutic approach, LVR remains relatively frequent and difficult to predict in clinical practice. Our aim was to identify new biomarkers of LVR and understand their involvement in its development.METHODS AND RESULTS:Proteomic analysis of plasma from the REVE-2 study (Remodelage Ventriculaire)-a study dedicated to the analysis of LVR which included 246 patients after a first anterior myocardial infarction-identified increased plasma levels of CLU (clusterin) in patients with high LVR. We used a rat model of myocardial infarction to analyze CLU expression in the LV and found a significant increase that was correlated with LVR parameters. We found increased CLU expression and secretion in primary cultures of rat neonate cardiomyocytes hypertrophied by isoproterenol. Silencing of CLU in hypertrophied neonate cardiomyocytes induced a significant decrease in cell size, ANP (atrial natriuretic peptide), and BNP (B-type natriuretic peptide) expression, associated with a decreased ERK (extracellular signal-regulated kinase) 1/2 activity, suggesting a prohypertrophic role of CLU. We then confirmed a significant increase of both intracellular p-CLU (precursor form of CLU) and m-CLU (mature form of CLU) in failing human hearts. Finally, the circulating levels of CLU (secreted form) were increased in patients with chronic heart failure who died from cardiovascular cause during a 3-year follow-up (n=99) compared with survivors (n=99).CONCLUSIONS: Our results show for the first time that plasma CLU levels are associated with LVR post-myocardial infarction, have in part a cardiac origin, and are a predictor of early death in heart failure patients

Circulating biomarkers of left ventricular remodeling after myocardial infarction

Le remodelage ventriculaire gauche (VG) en post-infarctus du myocarde (IDM) est associé à une augmentation du risque d’insuffisance cardiaque et de décès, mais il demeure difficile à prédire en pratique clinique.L’objectif principal de ma thèse était la recherche de biomarqueurs circulants du remodelage VG par l’approche protéine candidate et par protéomique différentielle dans la population REVE-2.Par l’approche protéine candidate, nous avons confirmé que le peptide natriurétique detype B (BNP) était un puissant facteur prédictif du remodelage VG en post-IDM. La métalloprotéase matricielle-8 (MMP-8), la MMP-9, l’hepatocyte growth factor (HGF), la Créactive protéine (CRP), la troponine I ont également fait la preuve de leur association.Par l’approche protéomique différentielle, en électrophorèse 2D différentielle en fluorescence (2D-DIGE), la clusterine a été identifiée comme biomarqueur potentiel,positivement associée au remodelage VG, nécessitant toutefois des travaux de confirmation.Par SELDI TOF MS, nous avons sélectionné 26 pics définis par leur rapport m/z, commebiomarqueurs potentiels du remodelage VG, dont 12 ont pu être identifiés et devrontdésormais être validés : le pic de m/z 2777 a été identifié comme le peptide N-terminal issu del’albumine après clivage par la pepsine. Les autres pics correspondraient à des fragments protéolytiques de protéines que sont le fibrinogène, le complément C3, C4 et C1q.La découverte de nouveaux biomarqueurs du remodelage VG devrait permettre d’améliorer la stratification du risque en post-IDM afin d’identifier les patients devant bénéficier d’un suivi plus rapproché et peut-être d’une prise en charge thérapeutique plus agressiveLeft ventricular (LV) remodelling after myocardial infarction (MI) indicates a high risk of heart failure and death but remains difficult to predict in clinical practice. Biomarkers may help to refine risk stratification. The main purpose was to find circulating biomarkers of LV remodelling after MI, using two strategies : candidate protein approach and differential proteomic approach, working on a population with a clearly defined phenotype, the REVE-2 study, a prospective multicenter study including 246 patients with a first anterior Q-wave MI. Blood samples were obtained at hospital discharge, at 1 month, 3 months and 1 year. An echocardiography was performed at the same time except for the 1st month to assess LVR.By candidate protein approach, we confirmed that B-type natriuretic peptide (BNP) was a powerful predictor of LV remodelling after MI. Additional biomarkers, such as matrix metalloproteinase-8 (MMP-8), MMP-9, hepatocyte growth factor (HGF), C-reactive protein (CRP) and cardiac troponin I were found to be associated with LV remodelling, highlighting several pathways implicated in pathophysiology of LV remodelling. We have also shown that biomarkers in association (BNP and cardiac troponin I, BNP and MMP-8, BNP and MMP-9) could improve risk stratification in post-MI by selecting groups of patients at higher risk.As the ideal biomarker was still not identified, we applied a differential proteomic approach, with no a priori hypothesis, in order to characterize proteomic signature of LV remodelling. The use of a protein enrichment kit, consisting of a library of combinatorial hexapeptide ligands, compressed the protein concentration range of plasma and serum, through the simultaneous onestep dilution of high-abundance and concentration of lowabundance proteins. Protein enrichment kit prior to two-dimensional (2D) electrophoresis or SELDI TOF MS (surface-enhanced laser desorption–ionization time of flight) analysis enabled the detection of proteins that were not detected in native blood sample and the accessibility to proteolytic fragments obtained from major proteins. Clusterin (apolipoprotein J) was identified as a potential biomarker of LV remodelling by 2D-DIfferential Gel Electrophoresis (2D-DIGE). Clusterin was quantified by Western blot and ELISA and was found to be positively associated with LV remodelling. However, this association was not found with all LV remodelling parameters nor at each time during the year following MI, requiring further analysis. Differential proteomic approach by SELDI TOF MS selected 26 m/z peaks, as potential biomarkers of LV remodelling. Of them, 12 were identified by mass spectrometry. The 2777 m/z peak was identified directly from the ProteinChip array as being the N-terminal peptide (24–48 aa) generated from albumin by pepsin cleavage. Other peaks were identified after purification using chromatographic columns or liquid-phase isoelectric focusing : most of them were found to be proteolytic fragments of proteins like fibrinogen, C3, C4 and C1q complement. Identifications have now to be validated with specific techniques, usually by immmunoprecipitation and Western blot analysis.Finding new biomarkers of LV remodelling could help refine risk stratification and identify patients in whom more aggressive therapy and/or more frequent follow-up could be needed

Introduction

International audienceCet article permet de prendre la mesure de la multiplicité des « transmodalisations » des contes des frères Grimm du XIXe siècle à aujourd'hui, et se conçoit comme un élargissement de l’aire géographique et des domaines artistiques abordés jusqu’ici par les travaux universitaires français sur les adaptations de contes, ouvrant le champ jusqu’au cinéma et à la musique contemporains, et l’horizon jusqu’au Liban et aux anciennes républiques de l’URSS. Il fournit un important état de la recherche sur la question, tandis que la fréquence à laquelle se succèdent les créations inspirées de contes atteste de la pertinence et de l’actualité sans cesse renouvelée de ce champ de recherche

Le Conte : d’un art à l’autre. Adaptation et devenir des contes populaires en Europe centrale et orientale (XIX-XXIe s.)

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Introduction

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Extracellular Matrix Turnover Biomarkers Predict Long-Term Left Ventricular Remodeling After Myocardial Infarction

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Serum MMP-8: a novel indicator of left ventricular remodeling and cardiac outcome in patients after acute myocardial infarction.

OBJECTIVE: Left ventricular (LV) remodeling following myocardial infarction (MI) is characterized by progressive alterations of structure and function, named LV remodeling. Although several risk factors such as infarct size have been identified, LV remodeling remains difficult to predict in clinical practice. Changes within the extracellular matrix, involving matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs), are an integral part of left ventricular (LV) remodeling after myocardial infarction (MI). We investigated the temporal profile of circulating MMPs and TIMPs and their relations with LV remodeling at 1 year and clinical outcome at 3 years in post-MI patients. METHODS: This prospective multicentre study included 246 patients with a first anterior MI. Serial echocardiographic studies were performed at hospital discharge, 3 months, and 1 year after MI, and analysed at a core laboratory. LV remodeling was defined as the percent change in LV end-diastolic volume (EDV) from baseline to 1 year. Serum samples were obtained at hospital discharge, 1, 3, and 12 months. Multiplex technology was used for analysis of MMP-1, -2, -3, -8, -9, -13, and TIMP-1, -2, -3, -4 serum levels. RESULTS: Baseline levels of MMP-8 and MMP-9 were positively associated with changes in LVEDV (P = 0.01 and 0.02, respectively). When adjusted for major baseline characteristics, MMP-8 levels remained an independent predictor LV remodeling (P = 0.025). By univariate analysis, there were positive relations between cardiovascular death or hospitalization for heart failure during the 3-year follow-up and the baseline levels of MMP-2 (P = 0.03), MMP-8 (P = 0.002), and MMP-9 (P = 0.03). By multivariate analysis, MMP-8 was the only MMP remaining significantly associated with clinical outcome (P = 0.02). CONCLUSION: Baseline serum MMP-8 is a significant predictor of LV remodeling and cardiovascular outcome after MI and may help to improve risk stratification