Rôle de l'homéostasie mitochondriale dans l'hypertension artérielle et l'anévrisme de l'aorte abdominale

Cardiovascular diseases are the leading cause of death worldwide, where primary arterial hypertension remains a major risk factor. A chronic rise in blood pressure has a detrimental effect on both microcirculation and macrocirculation, which can lead to pathologies such as abdominal aortic aneurysm (AAA). Unfortunately, the consequences of this disease are well known, unlike the initiating process. Through this thesis, we sought to characterize the relationship between mitochondrial dynamic dysfunction and arterial hypertension, both in resistance and compliance arteries using an OPA1+/- mouse model hypertensive to L-NAME or angiotensin II. We sought to understand the relationship between disruption of mitochondrial homeostasis as an initiating element and AAA caused by either a high-cholesterol (HCD) or high-fat (HFD) diet in LDLR-/- mice hypertensive due to angiotensin II infusion, and metabolomically characterized this pathology at the plasma and tissue level, to reveal potential prognostic markers. Our results revealed a protective role of the mitochondrial fusion protein OPA1 against pathological remodeling in the resistance arteries and exclusively in the abdominal aorta. In addition, our results demonstrated a more severe impairment of mitochondrial homeostasis in AAA induced by the HCD diet at tissue level, with decreased mitochondrial biogenesis and ATP synthase as well as increased mitochondrial mitophagy and fission. Also, mice suffering from this AAA showed a profound alteration of their metabolic profile at the aortic and plasma level,mainly centered on an alteration of nitric oxide, lipid, carbohydrate and amino acid metabolism.