Proteomic Profiling Identifies Infection-Associated Pathways in Pediatric Aortic Aneurysms

Abstract

Aortic aneurysm (AA) in children is a rare but life-threatening condition with poorly understood molecular mechanisms. To better understand AA in children, we conducted nanoliquid chromatography-tandem mass spectrometry analysis to compare protein differences in aortic tissue samples between AA patients and controls. Our proteomic analysis revealed significant enrichment of infection-associated immune pathways, accompanied by the upregulation of PRMT1, RIG-I, ISG15, and STING1, suggesting activation of innate immune signaling during pediatric AA development. Pathway enrichment analysis identified multiple pathways annotated as bacterial- and viral infection-related pathways, which may reflect activation of innate immune signaling or sterile inflammatory responses rather than direct evidence of active infection. Furthermore, proteomic profiling identified dysregulation of proteins involved in actin cytoskeleton organization and extracellular matrix remodeling, including increased expression of representative actin cytoskeleton-associated proteins and decreased expression of collagen-related proteins, suggesting structural alterations of the aortic wall. Collectively, these findings highlight the potential involvement of infection-associated innate immune signaling and immune dysregulation, providing novel insights into the molecular mechanisms underlying vascular remodeling and aneurysm formation.