Identification of Cardiac CircRNAs in Mice With CVB3-Induced Myocarditis

Abstract

Background: Viral myocarditis could initiate various immune response to the myocardium, resulting in myocyte damage and subsequent cardiac dysfunction. The expression profile and functions of circRNAs in this process are unknown.Methods: Fulminant myocarditis (FM) and non-FM models were induced by coxsackie B3 virus (CVB3) infection in A/J mice and C57BL/6 mice, respectively. CircRNAs expression profile was identified by RNA-seq. Quantitative RT-PCR, Spearman rank correlation, KEGG pathway, GO analysis, Western blot and flow cytometry were performed for functional analysis.Results: Severer inflammatory cell infiltration and cardiomyocyte necrosis were presented in CVB3-treated A/J mice than those in C57BL/6 mice. The dysregulated circRNAs in both of the mouse strains displayed strong correlation with the immune response, but dysregulated circRNAs in A/J mice were more prone to cardiac dysfunction. KEGG analysis indicated that the target genes of dysregulated circRNAs in A/J mice were mainly involved in viral infection, T cell and B cell receptor signaling pathways, while the target genes of dysregulated circRNAs in C57BL/6 mice were unrelated to immune pathways. Furthermore, knockdown of circArhgap32 that was downregulated in CVB3-treated A/J mice promoted cardiomyocyte apoptosis in vitro.Conclusion: Our data showed that cardiac circRNAs dysregulation is an important characteristic of viral myocarditis.

Noncoding RNAs and Cardiac Fibrosis

“…This suggested that lncRNA ROR plays an important role in chronic VMC [ 62 ]. Differential expression of circRNAs has been found in patients with fulminant myocarditis and in mice, and a bioinformatics analysis revealed the involvement of severely dysfunctional immune signaling pathways, including TNF and T-cell receptors, in VMC [ 76 , 77 ]. Compared to miRNAs, other lncRNAs and circRNAs, ncRNAs have not been studied in detail in the field of mechanistic development of VMC and may be potential biomarkers and therapeutic targets for VMC in the future.…”