Research On Exploring Differentially Expressed Genes With Calcification Mechanism Of Coronary Artery In-stent Restenosis Base On Bioinformatics

BackgroundCoronary atherosclerotic heart disease is a common and frequently-occurring disease which have threatened human health.Currently,drug-eluting stent implantation is a mainstay in the treatment of coronary heart disease,but some patients occur post-stent restenosis(ISR)after treatment.ISR is characterized by recurrent angina pectoris,or acute coronary syndrome in severe cases.ISR seriously affects the quality of life and clinical prognosis of patients,and is also a difficult problem for current treatment.Previous studies have shown that ISR is mainly caused by inflammation after vascular endothelial injury,and the accumulation of inflammatory factors induces the proliferation,differentiation and migration of vascular smooth muscle cells to form new intima and the deposition of extracellular matrix to lead to lumen stenosis.Despite the use of anti-endothelial drugs such as rapamycin or paclitaxel to treat ISR,the incidence of ISR in the real world is 10%.Combined with previous studies and observations of clinical data suggesting that calcification may play a role in ISR residual incidence,calcification may play a role in ISR residual incidence.ObjectiveThrough bioinformatics methods,the potential pathogenesis genes and pathways of calcification in ISR process were studied to provide theoretical basis for subsequent serological markers and drug therapy targets.MethodsISR related gene data were obtained from GEO database,and dataset GES12225 was selected as the research object.GES12225 included 3 ISR samples after PCI and 3 ISR samples without PCI.Limma data package of R language was used to homogenize and correct the original data.Differentially expressed genes(DEG)were screened by GE02R,and ID conversion and GO analysis of DEG were performed by DAVID database.Secondly,KOBAS database is used to analyze and visualize KEGG signal pathway of DEG.Finally,the protein interaction network(PPI)analysis of DEG was performed by STRING online software,the PPI results were visualized by C ytoscape software,and the core genes related to calcifi cation in the pathogenesis of ISR were screened by Cytohubba built-in plug-in.ResultsA total of 29618 coding genes of GES 12225 were homogeneously treated by LIMMA package.GE02R was used to screen the processed data,and a total of 135 differentially up-regulated and 253 differentially down-regulated genes were obtained.There were similarities among the differentially expressed genes data sources.GO analysis showed DEGs biological process(BP)is mainly involved in transcription regulation,differentiation of epithelial mesenchymal conversion regulation,osteogenesis regulation and molecular functions(MF)mainly involves DNA binding,combining,phosphorus,protein and nucleic acid,cell composition(CC)mainly concentrated in the microvilli,nucleus,myosin,irregular complex lining system.KEGG analysis found that signaling pathways closely related to ISR included Ubiquitin mediated proteolysis and PI3K-Akt signaling Pathway.PPI network and Cytohubba plug-in showed that the top 10 pathogenic genes were POLR2E,RUNX2,NANOG,FOX03,MRPS10,PCNA,MRPL32,BMP2,MRPS16 and MRPL57.RUNX family transcription factor 2(RUNX2)and bone morphogenetic protein 2(BMP2)are closely related to calcification.ConclusionRUNX2 and BMP2 may be closely related to the mechanism calcification of ISR,and may be potential diagnostic markers and therapeutic targets of I SR calcification.