MMP9, CXCR1, TLR6, and MPO participant in the progression of coronary artery disease

Abstract Coronary artery disease (CAD) is the most frequent cardiovascular disease, which is induced by the decreased myocardial blood supply. The present study is conducted to understand the mechanisms of CAD. The GSE98583, GSE69587, and GSE71226 datasets from the Gene Expression Omnibus database were obtained. The differentially expressed genes (DEGs) were analyzed by the limma package, then the DEGs appeared in two or three datasets were selected as the coregulated genes using the VENNY tool, followed by enrichment analysis using DAVID tool. Protein‐protein interaction (PPI) network, microRNA‐transcription factor‐target regulatory network, and drug‐gene network were visualized. Finally, quantitative PCR and dual‐luciferase reporter assay were conducted to validate the expression of key genes and the target relationship. There were 221 coregulated genes in GSE98583, GSE69587, and GSE71226. Besides, four pathways and 23 functional terms for co‐upregulated genes, and 11 functional terms for co‐downregulated genes were enriched. The degrees of PPI network nodes matrix metallopeptidase 9 (MMP9), C‐X‐C motif chemokine receptor 1 (CXCR1), toll‐like receptor 6 (TLR6), and myeloperoxidase (MPO) were relatively higher. Moreover, MPO could interact with MMP9, CXCR1, and TLR6 in the PPI network. In the regulatory network, TLR6 and MMP9 separately were targeted by miR‐3960 and v‐rel avian reticuloendotheliosis viral oncogene homolog A ( RELA ). Additionally, MMP9 , CXCR1 , and MPO were involved in the drug‐gene network. The expression of MMP9 , CXCR1 , TLR6 , and MPO were significantly upregulated in CAD samples than control, and miR‐3960 could bind to TLR6 to inhibit its expression. CXCR1 and MPO might be involved in the progression of CAD. Besides, miR‐3960 might function in the pathogenesis of CAD through targeting TLR6 , and RELA might exert its role in CAD via targeting MMP9 .