Jouenne Alexis

Cardiovascular (CV) diseases are one of the most important causes of mortality and morbidity in prediabetic and type 2 diabetic patients. Studies have also highlighted the greater susceptibility to cardiovascular pathologies in diabetic women compared to diabetic men. Interestingly, these sex-related differences pre-exist before the overt of type 2 diabetes, at a prediabetic state, but the mechanisms involved in this dimorphism are still poorly understood. The aim of this project will therefore be to characterize the prediabetic and type 2 diabetic heart using complementary male and female animal models and will focus on oxidative stress, mitochondrial and endothelial dysfunctions linked to hyperglycemia. The prediabetic study will be hold on rats submitted to HFS (prediabetic model) The two models studied are the high in fat and sugar diet (prediabetes model), and the Goto-Kakizaki rat, a type 2 diabetic model without obesity. We are also studying different therapeutic approaches (metabolic, antioxidant) in order to find the best sex specific strategy to limit CV complications associated with prediabetes and type 2 diabetes. A multimodal approach combining imaging techniques (MRI-cine, perfusion, regional deformation) and spectroscopy (SRM of P-31) by magnetic resonance is carried out and coupled with biochemical analyses. In vivo experiments are realized on the whole animal, ex vivo exploration on isolated perfused hearts (Langendorff model) and in vitro analyzes on frozen tissues. The combination of magnetic resonance techniques will provide morphological, functional and metabolic information that will characterize the prediabetic and type 2 diabetic heart. In order to deepen the study of these systemic pathologies, the expression of genes involved in metabolism and inflammation will be assessed in various tissues such as liver, adipose tissue and heart. This project aims to provide a better understanding of the mechanisms involved in mitochondrial and endothelial dysfunctions involved in sexual dimorphism linked to cardiovascular complications associated with prediabetes and type 2 diabetes.