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Bioinformatics Analysis The Gene Expression Profile Of Acute Myocardial Infarction

Posted on:2018-08-14Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y X YangFull Text:PDF
GTID:1314330542478900Subject:Emergency medicine
Abstract/Summary:PDF Full Text Request
Acute myocardial infarction(AMI)is one of common kind of coronary heart disease with high mortality and morbidity.Approximately 60% of the AMI patients is more than 65 years of age or older.The regular clinical manifestations of AMI have constant retrosternal pain,cardiac failure,atrial fibrillation and cardiac rupture.It is indicated that the number of AMI patients is increasing annually,and controlling the numnber of AMI patients and exploring the molecular mechanism of AMI are urgent to be solved.So far,to our known,the development of AMI is caused by several bad living habits,such as smoking,drinking and environmental factor.Recently,it has been indicated that genetic factors may also contribute to AMI.Since AMI is a disease which can be induced by both environmental factors and genetic factors,the study of AMI in gene and expressionlevel,and especially the relationship among the candidated genes,is still the primary stage.The reperfusion therapy combining using drugs be taken as the major methods for treating AMI.However,the effect is not very ideal for high remission rate and recurrence rate.With the development of DNA microarray and High-Throughput sequencing technology,a large of genomic sequence data is produced.As one of common major diseases,AMI is urgent need for thorough treatment;the research of microarray data related to AMI is becoming new trends and hot spots.In this study,we aimed at identifying several key genes which were related with AMI by using bioinformatics analysis,and it might provide references for gene therapy and drug therapy of AMI.In this study,we used three gene expression profiles of AMI to further bioinformatics analysis(GSE66360,GSE34198 and GSE48060 downloaded for GEO database).Firstly,we screened the differentially expressed genes(DEGs)in AMI samples.Second,the functional and pathway enrich analyze were.Then,in order to explore the correlation between those DEGs and their upstream transcriptons,the interaction network of protein-protein internet,TF-Target,miRNA-Target and TF-Target-miRNA were constructed,respectively.Finally,we validate that themRNA expression level of PRKACA and CAT by Quantitative Real-time PCR(qRT-PCR)in AMI patients.As a result,a total of 622 DEGs were screened between the AMI samples and healthy normal tissue,including 251 up-regulated DEGs and 371 down-regulated DEGs.From the GO and KEGG pathway enrichment analysis,it was showed that most genes were several gene annotation such as eukocyte activation,angiogenesis and cell cycle,mitochondrion.Besides,most genes were enriched in the chemokine signaling pathway,epithelial cell signaling in helicobacter pylori infection,Wnt signaling pathway,glutathione metabolismand mitogen-activated protein kinase signaling pathway.Our results showed that the genes as PRKACA,PHLPP2,PAK1,NCK1,MRE11 A,ADCY4,CAT,CSNK1 E,GPX3,GSTO2,GSTO1,CALM1,ERK5,S100 PBP,TNFRSF10B and NUP98,five transcription factors(MLXIPL,NR2F6,STAT3,Egr-1and MEF2A),as well as hsa-miR-30 c are associated with AMI.In addition,a significant up-regulation of PRCKACA transcription in the most of the ten AMI patients compared with ten normal peoples by qRT-PCR,but a significant down-regulation CAT transcription in the most of the ten AMI patients,consistent with chip results.In our results,those novel findings candidated genes,transcription factors and miRNA might contribute to the development of AMI or deteriorating of the diseases after AMI via participating in mediating inflammatory response,the formation of plaque and thrombus,angiogenesis,myocardial remodeling,myocardial fibrosis,as well as cell proliferation and apoptosis of myocardial cells.They might be closely related to the development of AMI,and they might be a novel targets for gene therapy and drug therapy for AMI by further studying.
Keywords/Search Tags:Acute myocardial infarction, gene microarray, differentially expressed gene, transcription factor, microRNA
PDF Full Text Request
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