Identification of Cardiac CircRNAs in Mice With CVB3-Induced Myocarditis
Xiang Nie1, Jiahui Fan1, Huihui Li1
1Division of Cardiology, Hubei Key Laboratory of Genetics and Molecular Mechanisms of Cardiological Disorders, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Insights
Viral myocarditis causes cardiac dysfunction through immune responses. Circular RNAs (circRNAs) are dysregulated in this condition, impacting viral infection and immune pathways, highlighting their role in heart disease.
Area of Science:
- Cardiovascular Research
- Virology
- Immunology
- Molecular Biology
Background:
- Viral myocarditis involves immune responses leading to myocyte damage and cardiac dysfunction.
- The role of circular RNAs (circRNAs) in viral myocarditis remains largely unexplored.
Purpose of the Study:
- To investigate the expression profile and functional significance of circRNAs in viral myocarditis.
- To compare circRNA dysregulation in different mouse models of viral myocarditis.
Main Methods:
- Induction of fulminant and non-fulminant myocarditis models using Coxsackie B3 virus (CVB3) in A/J and C57BL/6 mice.
- RNA sequencing for circRNA expression profiling.
- Quantitative RT-PCR, KEGG pathway analysis, GO analysis, Western blot, and flow cytometry for functional characterization.
Main Results:
- CVB3 infection induced more severe inflammation and necrosis in A/J mice compared to C57BL/6 mice.
- Dysregulated circRNAs correlated with immune responses, with those in A/J mice linked to cardiac dysfunction.
- KEGG analysis revealed target genes of dysregulated circRNAs in A/J mice were involved in viral infection and T/B cell signaling, unlike in C57BL/6 mice.
- Knockdown of downregulated circArhgap32 exacerbated cardiomyocyte apoptosis.
Conclusions:
- Cardiac circRNA dysregulation is a significant feature of viral myocarditis.
- Specific circRNAs are implicated in the immune response and pathogenesis of viral myocarditis, potentially contributing to cardiac dysfunction.
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.
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