Deciphering the Proteomic Landscape of Circulating Extracellular Vesicles in Human Abdominal Aortic Aneurysm

Abdominal aortic aneurysm (AAA) is the most prevalent and lethal form of arterial aneurysm, frequently manifesting asymptomatically until a catastrophic rupture occurs. While various diagnostic imaging tools and several potential biomarkers have been explored for the purpose of early AAA screening, the usage of liquid biopsy such as extracellular vesicles (EVs)‐carried protein for the early diagnosis of AAA is still being overlooked. In this study, we enrolled 18 AAA patients and nine healthy normal controls, including data from the National Drug Clinical Trial Organisation—Vascular Surgery (NDCTO) (in‐house cohort) and the Second Clinical Medical College, Jinan University (Shenzhen People’s Hospital) (external cohort). We employed Olink’s proximity extension assay (PEA) technology based on the plasma EV proteins and first comprehensively characterised the proteomics landscape in circulating EV underlying AAA disease development. A complex profile of differential EV proteins and EV protein–protein interactions network in AAA patients was identified. The differentially expressed EV proteins in AAA patients were found to be significantly associated with several enriched pathways, including the cellular response to cytokine stimuli, inflammatory response, and the regulation of the glucocorticoid receptor (GR) pathway. Moreover, five hub proteins were identified as being of particular significance: these were Interleukin‐4, Interleukin‐6, MCP‐1, Neurturin, and Oncostatin‐M. The Olink proteomics technique was utilised in order to identify these proteins. The significance of these proteins was further validated through Western blotting and enzyme‐linked immunosorbent assay (ELISA) in the external cohort. The five EV proteins displayed reliable performance and robustness for distinguishing AAA from healthy people, revealing high accuracy with AUC values of 0.760, 0.840, 0.800, 0.840, and 0.900, respectively. The present study has revealed the plasma EV proteins landscape within AAA and further uncovered their potential roles in the pathogenesis of the disease. This presents a new direction for clinical diagnosis and management of AAA. Consequently, these five EV proteins have the potential to serve as useful biomarkers for the diagnosis and prediction of AAA. Further research is warranted to explore their potential as therapeutic targets.