Circular RNAs Differential Expression Profile And Bioinformatics Analysis Between ST-segment Elevation Myocardial Infarction And Stable Coronary Artery Disease

Background According to clinical syndromes,coronary heart disease included stable coronary artery disease and acute coronary syndrome.There are three types consisted in stable coronary artery disease:chronic stable exertional angina,ischemic cardiomyopathy,and the stable phase following acute coronary syndrome.As a type of acute coronary syndrome,ST-segment elevation myocardial infarction is a clinical syndrome caused by acute ischemia and hypoxia of myocardial cells due to total or near-total occlusion of coronary arteries.Circular RNAs are noncoding RNAs with covalently closed circular structures.They played important roles in a variety of diseases due to their stability,evolutionary conservation,and tissue developmental specificity.The purpose of this study was to find out the differential expression profiles of circRNAs between STEMI and SCAD,and to explore the possible mechanism of differentially expressed circRNAs involved in ST-segment elevation myocardial infarction through GO analysis and KEGG pathway analysis.Methods We collected STEMI patients after PCI within 24 hours and stable coronary artery disease patients without PCI,admitted to Qilu Hospital of Shandong University from May 2021 to October 2021.STEMI patients accepted percutaneous coronary intervention within 24 hours,SCAD patients were never treated with PCI.Then,we seperated peripheral blood mononuclear cells for whole transcriptome high-throughput sequencing.Hierarchical clustering analysis was carried on the sequencing results,and GO analysis and KEGG pathway analysis were performed on the parental genes of disregulatedly expressed circular RNAs.According to the number of expressions and the degree of statistical difference in the enrolled patients,the circular RNAs whose parental genes related to the cardiovascular system were screened out.Then,the circRNAs-miRNAs-genes network was constructed and we collected new samples from the two groups to verify the differences by qRT-PCR.We predicted the miRNAs that consistent circRNAs may bind to,analyzed the pathophysiological process involved the miRNAs and upstream genes,explored the role of circRNAs in the progression of STEMI.Results 4650 significantly up-regulated circRNAs and 3746 significantly down-regulated circRNAs in STEMI group,compared with SCAD group,were selected through high-throughput sequencing.GO analysis of their parental genes showed that they were mainly involved in protein methylation,protein ubiquitination,and nuclear pore structure construction.The KEGG pathway analysis of the parental genes showed that they were mainly involved in processes such as endocytosis,endoplasmic reticulum protein synthesis and endotoxin-induced inflammatory response.We screened out 6 differentially expressed circRNAs(has-circ-0001127,has-circ-0001163,has-circ-0001518,has-circ-0003757,has-circ-0006628,has-circ-0132148)to construct circRNAs-miRNAs-genes network,5 circRNAs(has-circ-0001 127,has-circ-0001163,has-circ-0001518,has-circ-0003757,has-circ-0006628)were verified by qRT-PCR.We screened out eight miRNAs(hsa-miR-2355-3p,hsa-miR-4651,hsa-miR-4712-5p,hsa-miR-5006-3p,hsa-miR-501-5p,hsa-miR-608,hsa-miR-6505-3p and hsa-miR-770-5p)which may co-bind multiple circRNAs.According to the analysis of miRNAs and upstream genes,circRNAs may participate in the occurrence and development of STEMI by affecting the mitochondrial function of cardiomyocytes,thereby affecting the process of mitochondria-mediated apoptosis,and mediating the process of inflammatory response.Conclusion Circular RNAs are differentially expressed between STEMI and SCAD.Bioinformatics analysis of differentially expressed circRNAs showed that circRNAs may affect the pathophysiological process of STEMI by regulating apoptosis and mediating the process of inflammatory response.This provides an idea for the follow-up study of STEMI mechanism.