Screening Of Biomarkers For Ischemic Cardiomyopathy And Analysis Of Tanshinone ⅡA Drug Targets Based On Data Mining

Part IScreening biomarkers for ischemic cardiomyopathy based on bioinformatics methodsObjective:Potential biomarkers of ischemic cardiomyopathy were screened based on bioinformatics methods in order to provide basis for the diagnosis and treatment of ischemic cardiomyopathy.Methods:Based on the GEO database of NCBI website,the differentially expressed genes in healthy myocardium and ischemic cardiomyopathy were screened by R language.The differentially expressed genes were analyzed by gene ontology（GO）,Kyoto gene and genome encyclopedia（KEGG）and protein-protein interaction（PPI）,respectively,and ROC curves were drawn to verify the target genes.Results:Based on the high throughput data set GSE26887,135 up-regulated genes and124 down-regulated genes were obtained under the screening condition of|log₂FC|>1and P<0.01.GO and KEGG enrichment analysis showed that ischemic cardiomyopathy was related to the overexpression of RHOA,changes of extracellular matrix,oxidoreductase activity,regulation of inflammatory response,muscle system process,cardiac conduction system and so on.Conclusion:Ischemic cardiomyopathy was closely related to the change of extracellular matrix and oxidoreductase activity.The differential genes and hub gene obtained by screening may be the new targets of diagnosis and treatment.Part II Network pharmacology and molecular docking reveal the mechanism of Tanshinone ⅡA against Ischemic cardiomyopathyObjective:There is no effective treatment I for schemic cardiomyopathy（ICM）,The literature reports that the traditional Chinese medicine Tanshinone ⅡA（Tan ⅡA）has therapeutic efficacy.The study aimed to explore the possible molecular mechanism of Tan ⅡA against ICM by network pharmacology and molecular docking.Methods:Tan ⅡA and ICM-related targets were retrieved from public databases.Gene ontology（GO）,Kyoto Encyclopedia of Genes and Genomes（KEGG）enrichment analysis and protein-protein interaction（PPI）network were used to investigate the protein targets and mechanism.The binding activity of core targets and Tan ⅡA were verified by molecular docking.Results : A total of 20 overlapping target proteins between Tan ⅡA and ICM were screened.PPI network identified HSP90AA1,ATM,PTPN11,CSNK2A1,TERT,PRKDC,and CA2 as key pharmacological targets.The results of GO function enrichment analysis included cell cycle,cell aging,cellular senescence,smooth muscle cell proliferation.KEGG pathway analysis showed that nitrogen metabolism,NF-kappa B signaling pathway,cell cycle,Adherens junction,apoptosis,and JAK-STAT signaling pathway were associated with Tan ⅡA in ICM.Tan ⅡA plays a role in ICM treatment by intervening in a series of core targets（e.g.HSP90AA1,PTPN11 and CA2）.Conclusion : The present work initially clarified the effective therapeutic targets,biological processes,and signaling pathways of Tan ⅡA treatment of ICM,which lay a foundation for further research on the pharmacological effects of Tan ⅡA treat ICM.