Identification of Potential Plasma Biomarkers of Abdominal Aortic Aneurysm Using a Metabolomics Approach

In the aging population, abdominal aortic aneurysm (AAA) is a widespread and serious disease. Currently, there are no available biomarkers for diagnosing or treating AAA with drugs in clinical use. Uncovering the metabolic signatures of AAA may provide new insights into its pathogenesis and facilitate the identification of novel metabolic biomarkers.

In the present study, we applied high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS)-based metabolomics to analyze plasma samples from 76 AAA patients and 72 controls.

A total of 115 differentially abundant metabolites were identified, and these metabolites were mainly involved in retinol metabolism, glutathione metabolism, purine metabolism, D-amino acid metabolism, pantothenate and CoA biosynthesis, porphyrin metabolism, and sphingolipid metabolism. After biomarker screening in the discovery cohort and biomarker verification in the validation cohort, 28 potential metabolite biomarkers of AAA were identified. Further examination indicated that three metabolites, including 5-Delta-Hydroxybutyl Hydantoin, 2-Amino-4-[(2- hydroxy-1-oxopropyl) amino] butanoic acid, and 15(R),19(R)-hydroxy PGF2, showed remarkable sensitivity and specificity in diagnosing AAA, with AUC values of 0.997, 0.989, and 0.978, respectively.

This metabolomics study revealed distinct plasma metabolic profiles in AAA patients compared to controls, identifying 115 differentially abundant metabolites. These metabolites were primarily enriched in pathways including retinol metabolism, glutathione metabolism, and purine metabolism. Three metabolites-5-delta-hydroxybutyl hydantoin, 2-amino-4-[(2-hydroxy-1- oxopropyl) amino] butanoic acid, and 15(R),19(R)-hydroxy-PGF2α-were identified as novel potential biomarkers and showed excellent diagnostic performance in combination. The findings suggest that dysregulation of retinol metabolism, implicated in vascular homeostasis, and glutathione metabolism, linked to oxidative stress and ferroptosis, may play roles in AAA pathogenesis. Alterations in purine metabolism further support the involvement of inflammatory and oxidative processes. While these biomarkers show promise, their functional roles in AAA and clinical utility require validation in larger, multicenter prospective studies.

This study identified potential novel plasma biomarkers of AAA, which could contribute to the discovery of diagnostic biomarkers and therapeutic targets for this disease.