Soutenance de thèse Justine DHOT

Heart Failure with preserved Ejection Fraction (HFpEF) is one of the most common cardiovascular diseases in the world. Patients, often elderly women, have many co-morbidities such as high blood pressure, obesity, diabetes, pulmonary arterial hypertension, renal failure or anemia. To date the associated mortality and morbidity are high and no treatment is available. It is therefore necessary to understand the pathophysiological mechanisms involved, in order to identify new therapeutic targets. Over the last ten years, studies have highlighted low-grade inflammation as the cause of HFpEF. This inflammation is believed to lead to endothelial dysfunction and alterations in cardiac function.The objectives of my thesis were to characterize a new animal model of HFpEF triggered by endothelial dysfunction in order to identify therapeutic targets thereafter. We showed that the TgB3 rat develops diastolic dysfunction, characteristic of HFpEF, over the long term. In conclusion, we were able to show that the increase in the expression of the receptor B-adrenergique leads the increase in the production of NO and O2 that would be at the origin of the endothelial dysfunction and thus possibly of the HFpEF. Finally, thanks to a transcriptomic study in pathological animals, we have identified a potential target which is increased at circulating level. This target is currently being evaluated in the clinic as a potential biomarker of HFpEF.