Verification of ferroptosis and pyroptosis and identification of PTGS2 as the hub gene in human coronary artery atherosclerosis

Ferroptosis and pyroptosis have not been fully studied in atherosclerosis. We aimed to investigate the expression of ferroptosis-related and pyroptosis-related proteins in human coronary arteries and analyse correlation with severity of atherosclerosis and clarify the interactions between proteins and possible mechanisms of atherosclerosis. 40 human coronary artery specimens were employed. The atherosclerotic lesions were characterized by Haematoxylin and Eosin (H&E) staining. The expression of prostaglandin-endoperoxide synthase 2 (PTGS2), anti-acyl-CoA synthetase long-chain family member 4 (ACSL4), glutathione peroxidase 4 (GPX4), caspase-1, and NOD-like receptor protein 3 (NLRP3) were analysed by immunohistochemical assay. Correlations between expression of proteins and severity of atherosclerosis were assessed using Spearman correlation analysis. Bioinformatic and coexpression analyses were performed to study the possible pathways and interactions. In the present study, PTGS2, ACSL4, caspase-1, and NLRP3, were upregulated, while GPX4 was downregulated in the advanced stages of atherosclerosis. The severity of atherosclerosis was positively associated with the expression of PTGS2, ACSL4, caspase-1, and NLRP3 and negatively associated with the expression of GPX4. Biological processes of lipid metabolism and inflammation and C-type lectin receptor signaling pathway were enriched. The five proteins interacted with each other directly or indirectly and PTGS2 might be the hub gene of atherosclerosis. Ferroptosis and pyroptosis may regulate the occurrence and development of atherosclerosis. These findings may shed light on new ideas and potential targets for the prevention and treatment of coronary artery atherosclerosis and the proteins may be used as biomarkers for the severity of atherosclerosis.