Objective:Cardiac remodeling when myocardial infarction(MI)is achieved is an established prognostic factor for function-related damage and failure of hear that happen progressively.Tongguan Capsules(TGC),i.e.,a Chines...Objective:Cardiac remodeling when myocardial infarction(MI)is achieved is an established prognostic factor for function-related damage and failure of hear that happen progressively.Tongguan Capsules(TGC),i.e.,a Chinese herbal treatment with patent has been previously demonstrated its potential benefits in cardiac function,but little is known about related mechanisms.This study sought to isolate and characterize exosomal circRNA profiles from post-MI cardiac remodeling patients in response to TGC,and further explore the possible molecular mechanisms.Methods:Exosomes were isolated from the plasma and analyzed by the detection of protein marker expression and transmission electron microscopy.This study employed DESeq2 package within Bioconductor for exploring circRNAs and determining the circRNA with differential expressions.Co-expression investigation was performed with the use of a weighted correlation framework.An investigation was conducted on the molecular framework and channels of different circRNA based on the investigation system of the and Kyoto Encyclopedia of Genes and Genomes(KEGG)Gene Ontology(GO)channels.The prediction was conducted for circRNA-miRNA interactions on the basis of frequently employed target prediction software,and the framework was built with the use of Cytoscape software.Results:In total,33084 circRNAs were detected in all chromosomes and 10065 circRNAs were identified with the use of circBase.Of them,40,207 and 258 differentially expressed circRNAs were detected between the MI group and control,MI and TGC groups,and the control and TGC groups.The differentially expressed circRNAs between the MI group and control,MI group and TGC group,and control and TGC group were significantly enriched in microtubule nucleation(BP,GO:0007020),protein binding(MF,GO:0005515),regulation of natural killer cell mediated cytotoxicity(BP,GO:0042269)corresponding to the cell cycle(hsa04110),lysine degradation(hsa00310)and lysine degradation(hsa00310)in KEGG channel investigation.Module_darkorange2 indicated the most differentiation with other modules by WGCNA investigation.This study employed a total of 14 circRNAs and 8 miRNAs which have significant interactions with each other for building the circRNA-miRNA frameworks,which indicated that has-miR-619-5p,has-miR-1268a and hasmiR-1285‐3p were under the regulation of a higher amount of circRNAs as compared with other miRNAs.Conclusion:In conclusion,different mechanisms and channels participated in the pathological processes associated with cardiac remodeling following MI.The altered circRNAs are likely to be critical to the cardioprotection of TGC through the circRNA-miRNA frameworks.展开更多
文摘Objective:Cardiac remodeling when myocardial infarction(MI)is achieved is an established prognostic factor for function-related damage and failure of hear that happen progressively.Tongguan Capsules(TGC),i.e.,a Chinese herbal treatment with patent has been previously demonstrated its potential benefits in cardiac function,but little is known about related mechanisms.This study sought to isolate and characterize exosomal circRNA profiles from post-MI cardiac remodeling patients in response to TGC,and further explore the possible molecular mechanisms.Methods:Exosomes were isolated from the plasma and analyzed by the detection of protein marker expression and transmission electron microscopy.This study employed DESeq2 package within Bioconductor for exploring circRNAs and determining the circRNA with differential expressions.Co-expression investigation was performed with the use of a weighted correlation framework.An investigation was conducted on the molecular framework and channels of different circRNA based on the investigation system of the and Kyoto Encyclopedia of Genes and Genomes(KEGG)Gene Ontology(GO)channels.The prediction was conducted for circRNA-miRNA interactions on the basis of frequently employed target prediction software,and the framework was built with the use of Cytoscape software.Results:In total,33084 circRNAs were detected in all chromosomes and 10065 circRNAs were identified with the use of circBase.Of them,40,207 and 258 differentially expressed circRNAs were detected between the MI group and control,MI and TGC groups,and the control and TGC groups.The differentially expressed circRNAs between the MI group and control,MI group and TGC group,and control and TGC group were significantly enriched in microtubule nucleation(BP,GO:0007020),protein binding(MF,GO:0005515),regulation of natural killer cell mediated cytotoxicity(BP,GO:0042269)corresponding to the cell cycle(hsa04110),lysine degradation(hsa00310)and lysine degradation(hsa00310)in KEGG channel investigation.Module_darkorange2 indicated the most differentiation with other modules by WGCNA investigation.This study employed a total of 14 circRNAs and 8 miRNAs which have significant interactions with each other for building the circRNA-miRNA frameworks,which indicated that has-miR-619-5p,has-miR-1268a and hasmiR-1285‐3p were under the regulation of a higher amount of circRNAs as compared with other miRNAs.Conclusion:In conclusion,different mechanisms and channels participated in the pathological processes associated with cardiac remodeling following MI.The altered circRNAs are likely to be critical to the cardioprotection of TGC through the circRNA-miRNA frameworks.
