Impact of high-fat diet on mitochondrial dynamics in Abdominal Aortic Aneurysm

Abdominal aortic aneurysm (AAA) is an asymptomatic pathology, representing more than 75% of aortic aneurysms. It is characterized by a significant dilation of the aortic wall, which usually lead to severe complications as aneurysm rupture. Surgical repair (open or endovascular) is currently the only treatment available for AAA. As obesity is an established as a risk factor for cardiovascular disease, lipid metabolism involvement in AAA is not clearly understood. It would therefore be interesting to study its impact on mitochondrial dynamics, whose bioenergetic functions are necessary to maintain the function and integrity of the aortic wall. Our aim is to study the impact of lipid metabolism on mitochondrial dynamics in abdominal aortic aneurysm. We used a murine model of 6 months old of hypertensive Ldlr-/- male mice (angiotensin II, 1 mg/kg/day) fed with a standard diet (ND) or high-fat diet (HFD) for 28 days. Supra-renal abdominal aorta segment was removed to perform transcriptional and protein analysis (RT-qPCR and Western blot respectively) of the mitochondrial homeostasis actors. For HFD fed mice, we found an obvious obesity of Ldlr-/- hypertensive mice. Our results revealed a similar incidence of abdominal aortic aneurysm and mortality rate, between ND and HFD hypertensive Ldlr-/- mice. In these two groups, mice suffering from an abdominal aortic aneurysm showed a significant decrease, in mitochondrial fusion (Mfn1/2) and fission (Dnml1) transcript expression. Moreover, DRP1 protein expression and the mitophagy protein, PARKIN, are increased only in Ldlr-/- hypertensive ND mice. However, no significant difference was found with Ldlr-/- hypertensive HFD mice. These preliminary data suggest that the obesity observed in Ldlr-/- hypertensive mice by the HFD, has no impact on the development of the aortic aneurysm, as well as on mitochondrial homeostasis.