Identification of potential therapeutic targets from bioinformatic analysis of necroptosis and immune infiltration in acute myocardial infarction

Background: Acute myocardial infarction (AMI) is a serious, deadly disease with a high incidence. However, it remains unclear how necroptosis affects the pathophysiology of AMI. Using bioinformatic analyses, this study investigated necroptosis in AMI. Methods Using the Gene Expression Omnibus (GEO) database, we obtained the GSE66360 dataset related to AMI. Venn diagrams were used to identify necroptosis-related differential genes (NRDEGs). The genes with differential expression in AMI were analyzed using gene set enrichment analysis (GSEA), and a protein-protein interaction (PPI) network was established. A transcription factor prediction and enrichment analysis was conducted for the NRDEGs, and the relationships between AMI, NRDEGs, and immune cells were determined. Finally, in the additional dataset (GSE61145), NRDEG expression levels and immune infiltration were confirmed, and gene expression levels were further verified experimentally. Results GSEA revealed that necroptosis pathways were significantly enriched in AMI. We identified 10 NRDEGs, including TNF, TLR4, FTH1 and so on. Enrichment analysis indicated that the NOD-like receptor and TNF signaling pathways were significantly enriched. Four NRDEGs, FTH1 , IFNGR1 , STAT3 , and TLR4 , were identified; however, additional datasets and further experimental validation are required to confirm their roles. In addition, we determined that a high abundance of monocytes, macrophages, neutrophils, induced Tregs, and Th2 cells prompted AMI development. Conclusions In this study, four genes with potential to affect the development of AMI through necroptosis ( FTH1 , IFNGR1 , STAT3 , and TLR4 ) were identified. In addition, we found that a high abundance of monocytes, macrophages, neutrophils, and Th2 cells affected AMI. This helps determine the pathological mechanism of necroptosis and immune cells that influence AMI and provides a novel strategy for targeted therapy.