Studying On Differentially Expressed Genes In Myocardium Of Mice With Acute Myocardial Infarction Based On Bioinformatics Method

Objective: This study identifies differentially expressed genes(DEGs)in the myocardial tissue of mice with acute myocardial infarction and mice with non-myocardial infarction,aimed to provide a theoretical basis for exploring potential diagnostic biomarkers and novel therapeutic targets for acute myocardial infarction(AMI).Methods:(1)the microarray expression profiles of AMI were retrieved from the Gene Expression Omnibus(GEO)database and the datasets were selected according to the design of our study.The limma package,Robust Rank Aggreg package,Clusterprofiler package,and so on were installed in R language.The DEGs of each dataset were screened out based on the limma package in R language.Merging the DEGs of each dataset through the Robust Rank Aggreg package in R language,we obtained the shared DEGs of several datasets.The shared DEGs were performed Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis by using Clusterprofiler package.(2)in order to explore the correlation among the shared DEGs,protein-protein interaction(PPI)network was constructed using the STRING database.Utilizing the Molecular Complex Detection(MCODE)plug-in of Cytoscape,the functional module was constructed by clustering in the PPI network.Utilizing the Cyto Hubba plug-in,the hub genes were screened out.(3)mouse model with AMI(MI group)and non-infarcted mouse model(Sham operated group)were constructed.The m RNA expression levels of key DEGs in the myocardial tissue of mice with myocardial infarction and mice in sham operated group were verified by quantitative real-time polymerase chain reaction(q RT-PCR).Result: Three microarray datasets,including GSE775,GSE19322,and GSE97494,were screened out from the GEO database.2149 DEGs were obtained from the GSE775,including 23 down-regulated and 2126 up-regulated genes.597 DEGs were obtained from the GSE19322,including 446 down-regulated and 151up-regulated genes.4534 DEGs were obtained from the GSE97494,including 3879down-regulated and 655 up-regulated genes.The DEGs of three datasets were merged by the robust rank aggregation(RRA)method.We obtained 57 DEGs which were shared among three datasets,including 2 down-regulated and 55up-regulated genes.According to the GO functional analysis of 57 DEGs,the DEGs were mainly enriched in the following functional classification: receptor ligand activity,cytokine activity,cytokine receptor binding,G-protein coupled receptor binding,carbohydrate binding,chemokine activity,chemokine receptor binding,and so on.According to the KEGG pathway analysis of 57 DEGs,the DEGs were mainly enriched in IL-17 signaling pathway,cytokine-cytokine receptor interaction,chemokine signaling pathway,TNF signaling pathway,and so on.Using the MCODE plug-in of the Cytoscape software,the module analysis filtered out 18 key genes,including Cxcl5,Arg1,Cxcl1,Spp1,Selp,Ptx3,Tnfaip6,Mmp8,Serpine1,Ptgs2,Il6,Il1r2,Il1 b,Ccl3,Ccr1,Hmox1,Cxcl2,Ccl2.Ccr1 was the most fundamental gene in the PPI network.Using the Cyto Hubba plug-in of the Cytoscape software,4 hub genes in total were identified,including Cxcl1,Cxcl2,Cxcl5,and Mmp8.Finally,the m RNA high expression of Tnfaip6,Ptgs2 and Mmp8 was further verified in myocardial tissue of mice with acute myocardial infarction by q RT-PCR.Conclusion:(1)The expression levels of Tnfaip6,Ptgs2 and Mmp8 are significantly increased in myocardial tissue of mice with acute myocardial infarction,which may be closely associated with the occurrence and development of AMI.(2)Tnfaip6,Ptgs2 and Mmp8,especially the Ptgs2 which is enriched in IL-17 signaling pathway and TNF signaling pathway,may be potential diagnostic biomarkers or novel therapeutic targets for AMI,which needs to be further researched.