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

Utilisation des médicaments indiqués dans la maladie d'Alzheimer (analyse de données de remboursement)

BORDEAUX2-BU Santé (330632101) / SudocSudocFranceF

Non-coding RNAs in cardiac autophagy following myocardial infarction

International audienceMacroautophagy is an evolutionarily conserved process of the lysosome-dependent degradation of damaged proteins and organelles and plays an important role in cellular homeostasis. Macroautophagy is upregulated after myocardial infarction (MI) and seems to be detrimental during reperfusion and protective during left ventricle remodeling. Identify new regulators of cardiac autophagy may help to maintain the activity of this process and protect the heart from MI effects. Recently, it was shown that non-coding RNAs (microRNAs and long non-coding RNAs) are involved on autophagy regulation in different cell types including cardiac cells. In this review, we summarized the role of macroautophagy in the heart following MI and we focused on the non-coding RNAs and their targeted genes reported to regulate autophagy in the heart under these pathological conditions

Towards a model of wheat leaf morphogenesis at plant scale driven by organ-level metabolites

International audienceLeaf dimensions, specific mass and composition are traits of interest, as leaves constitute the main exchange surface with the aboveground environment. These variables arise from the interplay between many processes, and vary with growth conditions. Models of plant growth are useful tools to explore a wide range of climatic scenarios, management practices and genotypes. However, most models lacks process-based formalisms allowing simulating shoot architecture plasticity. We propose a functional-structural wheat model that couples carbon and nitrogen metabolism with leaf morphogenesis during the vegetative stage. The originality of our model relies on the interaction between leaf growth and the metabolism of carbon and nitrogen in the growing zone, which is possible thanks to an explicit and detailed formalism of the processes at organ level. The model simulates the appearance of successive leaves using coordination rules instead of a constant phyllochron as a driving mechanism. As a first step, main modules were evaluated separately: the coordination model and the metabolism model of a single growing leaf. The model shows interesting emergent properties: phyllochron stability, pattern of mature leaf length along the culm and realistic kinetics of length, dry mass and concentrations in both growing and mature zones. A qualitative evaluation strategy of the completely integrated model at plant scale is then proposed. As a conclusion, the model appears to be a useful concept, which could be transposed to other grasses

Proteomic Profiling of Macrophages by 2D Electrophoresis

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Modelling wheat shoot morphogenesis at plant scale from organ-level metabolites

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Interplay between phosphorylation and O-GlcNAcylation of sarcomeric proteins in ischemic heart failure Running title: Interplay between phosphorylation and O-GlcNacylation of sarcomeric proteins

International audiencePost-translational modifications (PTMs) of sarcomeric proteins could participate to left ventricular (LV) remodeling and contractile dysfunction leading in advanced heart failure (HF) with altered ejection fraction. Using an experimental rat model of HF (ligation of left coronary artery) and phosphoproteomic analysis, we identified an increase of desmin phosphorylation and a decrease of desmin ON -acetylglucosaminylation (O-GlcNAcylation). We aim to characterize interplay between phosphorylation and O-GlcNAcylation for desmin in primary cultures of cardiomyocyte by specific O-GlcNAcase (OGA) inhibition with thiamet G and silencing O-GlcNAc transferase (OGT) and, in perfused heart perfused with thiamet G in sham-and HF-rats. In each model, we found an efficiency of O-GlcNAcylation modulation characterized by the levels of O-GlcNAcylated proteins and OGT expression (for silencing experiments in cells). In perfused heart, we found an improvement of cardiac function under OGA inhibition. But none of the treatments either in in vitro or ex vivo cardiac models, induced a modulation of desmin, phosphorylated and O-GlcNAcylated desmin expression, despite the presence of O-GlcNAc moities in cardiac desmin. Our data suggests no interplay between phosphorylation and O-GlcNAcylation of desmin in HF post myocardial infarction. The future requires finding the targets in heart involved in cardiac improvement under thiamet G treatment