Zhetao Li,1 Wansong Zhao,2 Wenbo Ji,3 Zhaoshui Li,1 Kuo Wang,4 Ting Jiang1 

1Heart Center, Qingdao Hiser Hospital Affiliated of Qingdao University (Qingdao Traditional Chinese Medicine Hospital), Qingdao, People’s Republic of China; 2Operating Room Department, Qingdao Municipal Hospital, Qingdao, People’s Republic of China; 3Operating Room Department, Qingdao Hiser Hospital Affiliated of Qingdao University (Qingdao Traditional Chinese Medicine Hospital), Qingdao, People’s Republic of China; 4Preventive and Health Care Department, Qingdao Hiser Hospital Affiliated of Qingdao University (Qingdao Traditional Chinese Medicine Hospital), Qingdao, People’s Republic of China

Correspondence: Ting Jiang; Kuo Wang, Email jiangting@qdu.edu.cn; wangkuo4321@163.com

Background: Coronary atherosclerosis (CA) is a major cause of coronary artery disease (CHD), with inflammation significantly influencing its pathogenesis. This study explores the role of neutrophil extracellular traps (NETs) in CA to understand their influence on disease progression.
Methods: Using the GEO database, we analyzed RNA expression microarray data from CA patients, identifying NET-related differentially expressed genes (NETDEGs) through logistic regression, SVM, and LASSO operator regression analyses. CA samples were categorized into risk subgroups based on gene traits, with further analysis on the biological characteristics and immune cell infiltration of the high-risk subgroup. Additionally, transcription factor (TF)-gene, microRNA (miRNA)-gene, and RNA binding protein (RBP)-gene regulatory networks were investigated, alongside a protein-drug network to propose potential targeting therapies. Expression levels of NETDEGs were validated via qRT-PCR and Western blotting.
Results: Three NETDEGs—MMP9, ERN1, and G0S2—were pinpointed as key players in CA development, regulated by TFs, miRNAs, and RBPs. These genes defined high-risk subgroups marked by intense inflammatory signaling and apoptosis. High neutrophil infiltration correlated positively with NETDEG expression in CA samples, supporting their potential as biomarkers. MMP9 emerged as a notable drug target, providing a possible therapeutic avenue.
Conclusion: This research highlights an independent NETDEG trait in CA, offering insights into potential biomarkers and therapeutic targets for combating this disease.

Keywords: neutrophil extracellular traps, coronary atherosclerosis, biomarker, therapy target