Identification of marophage-related biomarkers in acute myocardial infarction (AMI) by bioinformatic analysis and clinical validation Running title: Macrophage-related biomarkers in AMI

Abstract

Abstract Background Although reperfusion therapy is widely performed in patients with acute myocardial infarction (AMI), the residual risk of poor prognosis remains substantial. As important immune cells involved in the body's inflammatory response, macrophages are differentiated from monocytes that have been recruited to tissues, and their polarisation status has a significant impact on the development and prognosis of AMI. There are no recognised macrophage-associated key regulators that play an important role in the development of AMI. Objective The study aimed to identify potential biomarkers associated with macrophages for the early recognition and intervention of AMI. Methods and results Three datasets which can be obtained publicly (GSE48060, GSE66360, and GSE97320 datasets) from the Gene Expression Omnibus (GEO) database were analysed to identify differentially expressed genes (DEGs) using peripheral blood tissue samples from 83 AMI patients and 74 normal individuals. Subsequent WGCNA analysis was performed and 387 genes with the most significant correlations with macrophages were identified. Then, intersecting 192 DEGs with 387 genes from WGCNA, a total of 151 overlapping genes were found. Protein-protein interaction (PPI) network analysis were performed to identify the hub genes. Further we recruited 44 individuals and colleted blood samples to validate the stability and reliability of the predicted hub tragets toll-like receptor 2 (TLR2), toll-like receptor 2 (TLR4), toll-like receptor 8 (TLR8), matrix metalloproteinase 9 (MMP9) and tyrosine kinase binding protein (TYROBP) using qRT-PCR assay. As a result, TLR2, TLR4, TLR8, MMP9 and TYROBP were identified as the marophage-related biomarkers in AMI. Conclusions The macrophage-related genes TLR2, TLR4, TLR8, MMP9 and TYROBP may enable timely detection of AMI, leading to prompt intervention and better prognosis.