Study On Exploring Differentially Expressed Genes With Myocardial Infarction Based On Bioinformatics

Background:Acute myocardial infarction(AMI)refers to the necrosis of myocardial cells with coronary artery occlusion,myocardial ischemia and hypoxia caused by atherosclerotic plaque rupture and thrombosis.It is one of the main causes of human death in today's society.Despite nowdays rapid progress in diagnosis and treatment of AMI,its mechanism remains to be further explored,and the clinical treatment and prevention of AMI still have limitations.It is of great significance to further understand the genetic changes associated with MI and find the exact biomarkers for diagnosis and treatment.Previous studies have shown that gene expressions vary at different stages of cardiovascular disease.Those expressions are involved in the pathological process of AMI,and some are able to predict card:iovascular events.The bioinformatics analysis of genetic microarray provides a better way to elucidate the possible mechanisms of MI from the perspective of gene regulation.Gene expression profiling can provide enough information about the expression changes of genes associated with MI.Objective:This study that identify and validate differentially expressed genes(DEGs)in myocardial infarction(MI)samples via bioinformatics methods,aims to find potentialbiomarkers for the diagnosis and treatment of AMI;Analyze the possible mechanism of those genes in the pathogenesis,and find its potential role in the treatment of AMIL Materials and Methods:The microarray data of two separate datasets GSE66360 and GSE48060 of acute myocardial infarction(AMI)patients were downloaded from Gene Expression Omnibus(GEO)database.The DEGs between the control group and the AMI group were identified by the limma package.Then,Gene Ontology(GO)and Kyotoencyclopedia of genes and genomes(KEGG)were performed to analyze the function and to observe the pathways enrichment of those DEGs.After that,the protein-protein interaction(PPI)network was constructed by database STRING and visualized via software Cytoscape.Afterwords,the correlation between the previously screened key genes and myocardial infarction was then verified by an additional datasets GSE60993 downloaded from GEO.Finally,peripheral blood samples from patients with acute myocardial infarction that were tested by RT-qPCR to further validate the key genes.Results:A total of 1673 DEGs(FC>2,p<0.05)were indentified in Dataset GSE66360(including 49 AMI patients and 50 healthy controls),which comprised 918 up-and 755 down-regulated DEGs.A total of 1677 DEGs(FC>1.2,p<0.05)were indentified in Dataset GSE48060(including 31 AMI patients and 21 healthy controls),which comprised 441 up-and 1236 down-regulated DEGs.Venn diagram was applied to compare the DEGs of the two datasets,identifying 414 common DEGs.And GO was conducted to analyze the biological process(BP)of the 414 common DEGs,which were found significantly enriched in the inflammatory response and immune response process.Molecular function(MF)mainly involved in protein binding,nucleic acid binding,etc.The cellular component(CC)primarily concentrated in the lipopolysaccharide receptor complex and nucleoplasm.KEGG pathway enrichmentanalyses indicated that DEGs play a major role in pathways such as B cell receptor signaling,apoptosis,toll-like receptor signaling pathway,etc.Then,37 key genes(degree>10)were screened by PPI networkand then verified by GSE60993 dataset,compared with the control group,the expression levels of TLR2,MMP9 and S100A8 were significantly increased in AMI patients,and was gradually decreased in STEMI group,NSTEMI group,UA group and normal control group.Finally,The expression levels of TLR2,MMP9 and S100A8 were significantly increased in AMI patients via RT-qPCR which indicate that they are closely related to the occurrence and development of AMI.Conclusion:1.The expression levels of TLR2,MMP9 and S100A8 were significantly increased in patients with acute myocardial infarction,which was closely related to the occurrence and development of myocardial infarction.2.TLR2,MMP9,S100A8 may be potential diagnostic markers of acute myocardial infarction,and have the opportunity to become a potential therapeutic target for AMI,but further research is needed.