Metabolomic Profiling of Angiotensin-II-Induced Abdominal Aortic Aneurysm in Ldlr-/- Mice Points to Alteration of Nitric Oxide, Lipid, and Energy Metabolisms.

Abstract

Aneurysm is the second-most common disease affecting the aorta worldwide after atherosclerosis. While several clinical metabolomic studies have been reported, no study has reported deep metabolomic phenotyping in experimental animal models of aortic aneurysm. We performed a targeted metabolomics study on the blood and aortas of an experimental mice model of aortic aneurysm generated by high-cholesterol diet and angiotensin II in Ldlr−/− mice. The mice model showed a significant increase in media/lumen ratio and wall area, which is associated with lipid deposition within the adventitia, describing a hypertrophic remodeling with an aneurysm profile of the abdominal aorta. Altered aortas showed increased collagen remodeling, disruption of lipid metabolism, decreased glucose, nitric oxide and lysine metabolisms, and increased polyamines and asymmetric dimethylarginine (ADMA) production. In blood, a major hyperlipidemia was observed with decreased concentrations of glutamine, glycine, taurine, and carnitine, and increased concentrations of the branched amino acids (BCAA). The BCAA/glycine and BCAA/glutamine ratios discriminated with very good sensitivity and specificity between aneurysmatic and non-aneurysmatic mice. To conclude, our results reveal that experimental induction of aortic aneurysms causes a profound alteration in the metabolic profile in aortas and blood, mainly centered on an alteration of NO, lipid, and energetic metabolisms.