Characterising NETs-associated biomarkers and molecular clusters in atherosclerosis

Atherosclerosis, a persistent inflammatory-driven condition, has a key role in cardiovascular diseases. Recent studies suggest that neutrophil extracellular traps (NETs) contribute significantly to the progression of atherosclerosis, yet it is unclear what molecular mechanisms underlie this process. This study aims to investigate gene co-expression networks to identify gene modules associated with NET formation in atherosclerosis. Using publicly available transcriptomic data from carotid atherosclerotic plaque samples and adjacent tissue samples serving as controls, we analysed gene expression profiles to identify differentially expressed genes (DEGs) and their associated pathways. Functional enrichment and co-expression network analysis, identified a gene module linked to NET formation in atherosclerosis. This observation was further supported by an independent validation cohort, which confirmed the association of the identified module with NET formation in atherosclerosis. Notably, one gene module associated with NET formation exhibited a strong correlation with immune responses and inflammatory pathways. Remarkably, hub genes in NET formation such as CTSB, CD68, SIGLEC9, MAPK13, and HEXB emerged as central players in disease progression, despite showing no involvement in NET formation in control samples. These findings provide that NETs play a crucial role in fostering inflammation and plaque development, offering new insights into the molecular mechanisms underlying atherosclerosis. This study not only deepens our understanding of NET-mediated processes in atherosclerosis but also highlights potential biomarkers and therapeutic targets for mitigating NET-related vascular damage.