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METAPROFIL
Metabolic Programming of Atrial Fibrillation
FunderFrench National Research Agency (ANR)
Funder Contribution €841,747.00
DurationFrom 01 Oct 2024
Project codeANR-24-CE17-2243
Identifiers
Description
Atrial fibrillation (AF) is the most common arrhythmia worldwide, with high morbi-mortality rate, and for which obesity and related endothelial dysfunction are major risk factors. Brain-derived neurotropic factor (BDNF), a neuronal growth factor, regulates eating behavior and autonomic activities, all being affected during metabolic disease. Level of BDNF is diminished in type 2 diabetes and obesity, both in clinics and preclinical models. Decreased BDNF is closely associated with the development and outcome of cardiovascular diseases. Low dose BDNF therapy reduces the arrhythmic burden and recurrence of AF. While BDNF is expressed in endothelial cells (EC), a recent work highlighted BDNF limits NLRP3 inflammasome-induced pyroptosis and glucose metabolism reprogramming in vascular EC, an important cause of endothelial damages. Thus, BDNF appears as a key target to connect metabolic alterations to atrial cardiomyopathy. However, it is unclear if the decreased level of BDNF in EC during metabolic diseases leads to increased susceptibility to AF. Team#1 has developed an original relevant model of long-lasting metabolic syndrome in mice, induced by the “programming” effect of postnatal overfeeding (PNOF). With Team#1, recent unpublished data obtained by Team#2 show that this model develops AF. Based on preliminary data, we hypothesize that obesity-induced decrease in endothelial BDNF leads to AF. We aim to (i) establish the link between atrial EC and cardiac cells BDNF expression and the occurrence of AF in PNOF- and EC-BDNF-/- mice; (ii) rescue EC BDNF level in PNOF-induced AF using endothelial targeted microvesicles; (iii) link BDNF circulating levels to metabolic features of atrial cardiomyopathy in patients with AF (before/after ablation). Our results will help to understand the homeostatic role of endothelial BDNF at atrial level and involvement of its lowering on atrial cardiomyopathy occurring during metabolic disease.
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Atrial fibrillation (AF) is the most common arrhythmia worldwide, with high morbi-mortality rate, and for which obesity and related endothelial dysfunction are major risk factors. Brain-derived neurotropic factor (BDNF), a neuronal growth factor, regulates eating behavior and autonomic activities, all being affected during metabolic disease. Level of BDNF is diminished in type 2 diabetes and obesity, both in clinics and preclinical models. Decreased BDNF is closely associated with the development and outcome of cardiovascular diseases. Low dose BDNF therapy reduces the arrhythmic burden and recurrence of AF. While BDNF is expressed in endothelial cells (EC), a recent work highlighted BDNF limits NLRP3 inflammasome-induced pyroptosis and glucose metabolism reprogramming in vascular EC, an important cause of endothelial damages. Thus, BDNF appears as a key target to connect metabolic alterations to atrial cardiomyopathy. However, it is unclear if the decreased level of BDNF in EC during metabolic diseases leads to increased susceptibility to AF. Team#1 has developed an original relevant model of long-lasting metabolic syndrome in mice, induced by the “programming” effect of postnatal overfeeding (PNOF). With Team#1, recent unpublished data obtained by Team#2 show that this model develops AF. Based on preliminary data, we hypothesize that obesity-induced decrease in endothelial BDNF leads to AF. We aim to (i) establish the link between atrial EC and cardiac cells BDNF expression and the occurrence of AF in PNOF- and EC-BDNF-/- mice; (ii) rescue EC BDNF level in PNOF-induced AF using endothelial targeted microvesicles; (iii) link BDNF circulating levels to metabolic features of atrial cardiomyopathy in patients with AF (before/after ablation). Our results will help to understand the homeostatic role of endothelial BDNF at atrial level and involvement of its lowering on atrial cardiomyopathy occurring during metabolic disease.
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Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. 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Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. 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Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. 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Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. Provider Academic Bibliometrics & Assessment Computational Utility Service Expiration Session Name greekSession Description Stores the user session ID for Academic Bibliometrics & Assessment Computational Utility Service. 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