Identifying nexilin as a central gene in neutrophil-driven abdominal aortic aneurysm pathogenesis.

OBJECTIVES

Abdominal aortic aneurysm (AAA) is an inflammation-driven disease in which neutrophil infiltration is critical to its progression. This study aims to explore the molecular mechanisms behind neutrophil infiltration in AAA and identify key regulatory genes.

METHODS

We utilized weighted gene co-expression network analysis (WGCNA) and differential gene expression analysis to compare AAA and healthy abdominal aortic tissues. Functional enrichment analysis and a protein-protein interaction (PPI) network were constructed to understand gene functions. Machine learning algorithms were applied to identify key hub genes, followed by in vivo validation using an ApoE-/- mouse model.

RESULTS

Neutrophils, NK cells, and pDCs were significantly increased in AAA tissues. WGCNA identified 234 genes associated with neutrophil infiltration, of which 39 were significantly differentially expressed. Functional enrichment analysis highlighted roles in actin-related processes and pathways. Nexilin (NEXN) was consistently identified as a key hub gene negatively correlated with immune cell infiltration. In vivo validation confirmed that NEXN inhibits AAA progression in ApoE-/- mice by regulating immune cell infiltration.

CONCLUSION

NEXN plays a crucial role in modulating neutrophil infiltration in AAA. These findings provide new molecular insights into AAA pathogenesis and suggest NEXN as a potential target for AAA therapy.