CE34 - Contaminants, écosystèmes et santé

Impact of pollutants and AHR signaling on cardiac function in predisposed-models of cardiomyopathy – POPHeart

Submission summary

The interaction of pollutants with cardiac disease has only recently emerged. 2,3,7,8- tetrachlorodibenzo-p-dioxin (TCDD) is the most toxic and persistent organic pollutant that bioaccumulates in the body through the food chain. The toxicity of TCDD is mediated by the activation of Aryl Hydrocarbon Receptor (AHR), a ligand-activated transcription factor regulating detoxification enzyme expression. In healthy animals, TCDD exposure has been shown to induce mild cardiac hypertrophy. However, it remains unclear whether long-term TCDD exposure exacerbates heart dysfunction in models with predisposed risk factors for cardiomyopathy and what are the mechanism underlying TCDD cardiotoxicity. The aim of the project is to determine the cellular and molecular cardiotoxicity of chronic and low dose exposure to TCDD in two vulnerability conditions (aging & diabetes) in rodents, to analyze wether TCDD-induced cardiotoxicity is sex-dependent and to test whether AHR antagonists could reverse the cardiotoxic effects of TCDD in diabetic cardiomyopathy.

Project coordination

Marianne GERVAIS (Université Paris-Est Créteil)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

UPEC Université Paris-Est Créteil
CARPAT SIGNALISATION ET PHYSIOPATHOLOGIE CARDIOVASCULAIRE
EnVI NOUVELLES CIBLES PHARMACOLOGIQUES DE LA PROTECTION ENDOTHELIALE ET DE L'INSUFFISANCE CARDIAQUE

Help of the ANR 612,640 euros
Beginning and duration of the scientific project: September 2021 - 48 Months

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