DataSheet1_Identification of Cardiac CircRNAs in Mice With CVB3-Induced Myocarditis.docx

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.</p

Table1_Identification of Cardiac CircRNAs in Mice With CVB3-Induced Myocarditis.docx

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.</p

DataSheet_1_Expression Profiles and Potential Functions of Long Non-Coding RNAs in the Heart of Mice With Coxsackie B3 Virus-Induced Myocarditis.zip

AimsLong non-coding RNAs (lncRNAs) are critical regulators of viral infection and inflammatory responses. However, the roles of lncRNAs in acute myocarditis (AM), especially fulminant myocarditis (FM), remain unclear.MethodsFM and non-fulminant myocarditis (NFM) were induced by coxsackie B3 virus (CVB3) in different mouse strains. Then, the expression profiles of the lncRNAs in the heart tissues were detected by sequencing. Finally, the patterns were analyzed by Pearson/Spearman rank correlation, Kyoto Encyclopedia of Genes and Genomes, and Cytoscape 3.7.ResultsFirst, 1,216, 983, 1,606, and 2,459 differentially expressed lncRNAs were identified in CVB3-treated A/J, C57BL/6, BALB/c, and C3H mice with myocarditis, respectively. Among them, 88 lncRNAs were commonly dysregulated in all four models. Quantitative real-time polymerase chain reaction analyses further confirmed that four out of the top six commonly dysregulated lncRNAs were upregulated in all four models. Moreover, the levels of ENSMUST00000188819, ENSMUST00000199139, and ENSMUST00000222401 were significantly elevated in the heart and spleen and correlated with the severity of cardiac inflammatory infiltration. Meanwhile, 923 FM-specific dysregulated lncRNAs were detected, among which the levels of MSTRG.26098.49, MSTRG.31307.11, MSTRG.31357.2, and MSTRG.32881.28 were highly correlated with LVEF.ConclusionExpression of lncRNAs is significantly dysregulated in acute myocarditis, which may play different roles in the progression of AM.</p

DataSheet_5_Expression Profiles and Potential Functions of Long Non-Coding RNAs in the Heart of Mice With Coxsackie B3 Virus-Induced Myocarditis.zip

AimsLong non-coding RNAs (lncRNAs) are critical regulators of viral infection and inflammatory responses. However, the roles of lncRNAs in acute myocarditis (AM), especially fulminant myocarditis (FM), remain unclear.MethodsFM and non-fulminant myocarditis (NFM) were induced by coxsackie B3 virus (CVB3) in different mouse strains. Then, the expression profiles of the lncRNAs in the heart tissues were detected by sequencing. Finally, the patterns were analyzed by Pearson/Spearman rank correlation, Kyoto Encyclopedia of Genes and Genomes, and Cytoscape 3.7.ResultsFirst, 1,216, 983, 1,606, and 2,459 differentially expressed lncRNAs were identified in CVB3-treated A/J, C57BL/6, BALB/c, and C3H mice with myocarditis, respectively. Among them, 88 lncRNAs were commonly dysregulated in all four models. Quantitative real-time polymerase chain reaction analyses further confirmed that four out of the top six commonly dysregulated lncRNAs were upregulated in all four models. Moreover, the levels of ENSMUST00000188819, ENSMUST00000199139, and ENSMUST00000222401 were significantly elevated in the heart and spleen and correlated with the severity of cardiac inflammatory infiltration. Meanwhile, 923 FM-specific dysregulated lncRNAs were detected, among which the levels of MSTRG.26098.49, MSTRG.31307.11, MSTRG.31357.2, and MSTRG.32881.28 were highly correlated with LVEF.ConclusionExpression of lncRNAs is significantly dysregulated in acute myocarditis, which may play different roles in the progression of AM.</p

DataSheet_7_Expression Profiles and Potential Functions of Long Non-Coding RNAs in the Heart of Mice With Coxsackie B3 Virus-Induced Myocarditis.zip

AimsLong non-coding RNAs (lncRNAs) are critical regulators of viral infection and inflammatory responses. However, the roles of lncRNAs in acute myocarditis (AM), especially fulminant myocarditis (FM), remain unclear.MethodsFM and non-fulminant myocarditis (NFM) were induced by coxsackie B3 virus (CVB3) in different mouse strains. Then, the expression profiles of the lncRNAs in the heart tissues were detected by sequencing. Finally, the patterns were analyzed by Pearson/Spearman rank correlation, Kyoto Encyclopedia of Genes and Genomes, and Cytoscape 3.7.ResultsFirst, 1,216, 983, 1,606, and 2,459 differentially expressed lncRNAs were identified in CVB3-treated A/J, C57BL/6, BALB/c, and C3H mice with myocarditis, respectively. Among them, 88 lncRNAs were commonly dysregulated in all four models. Quantitative real-time polymerase chain reaction analyses further confirmed that four out of the top six commonly dysregulated lncRNAs were upregulated in all four models. Moreover, the levels of ENSMUST00000188819, ENSMUST00000199139, and ENSMUST00000222401 were significantly elevated in the heart and spleen and correlated with the severity of cardiac inflammatory infiltration. Meanwhile, 923 FM-specific dysregulated lncRNAs were detected, among which the levels of MSTRG.26098.49, MSTRG.31307.11, MSTRG.31357.2, and MSTRG.32881.28 were highly correlated with LVEF.ConclusionExpression of lncRNAs is significantly dysregulated in acute myocarditis, which may play different roles in the progression of AM.</p

Table_1_Expression Profiles and Potential Functions of Long Non-Coding RNAs in the Heart of Mice With Coxsackie B3 Virus-Induced Myocarditis.docx

AimsLong non-coding RNAs (lncRNAs) are critical regulators of viral infection and inflammatory responses. However, the roles of lncRNAs in acute myocarditis (AM), especially fulminant myocarditis (FM), remain unclear.MethodsFM and non-fulminant myocarditis (NFM) were induced by coxsackie B3 virus (CVB3) in different mouse strains. Then, the expression profiles of the lncRNAs in the heart tissues were detected by sequencing. Finally, the patterns were analyzed by Pearson/Spearman rank correlation, Kyoto Encyclopedia of Genes and Genomes, and Cytoscape 3.7.ResultsFirst, 1,216, 983, 1,606, and 2,459 differentially expressed lncRNAs were identified in CVB3-treated A/J, C57BL/6, BALB/c, and C3H mice with myocarditis, respectively. Among them, 88 lncRNAs were commonly dysregulated in all four models. Quantitative real-time polymerase chain reaction analyses further confirmed that four out of the top six commonly dysregulated lncRNAs were upregulated in all four models. Moreover, the levels of ENSMUST00000188819, ENSMUST00000199139, and ENSMUST00000222401 were significantly elevated in the heart and spleen and correlated with the severity of cardiac inflammatory infiltration. Meanwhile, 923 FM-specific dysregulated lncRNAs were detected, among which the levels of MSTRG.26098.49, MSTRG.31307.11, MSTRG.31357.2, and MSTRG.32881.28 were highly correlated with LVEF.ConclusionExpression of lncRNAs is significantly dysregulated in acute myocarditis, which may play different roles in the progression of AM.</p

DataSheet_3_Expression Profiles and Potential Functions of Long Non-Coding RNAs in the Heart of Mice With Coxsackie B3 Virus-Induced Myocarditis.zip

AimsLong non-coding RNAs (lncRNAs) are critical regulators of viral infection and inflammatory responses. However, the roles of lncRNAs in acute myocarditis (AM), especially fulminant myocarditis (FM), remain unclear.MethodsFM and non-fulminant myocarditis (NFM) were induced by coxsackie B3 virus (CVB3) in different mouse strains. Then, the expression profiles of the lncRNAs in the heart tissues were detected by sequencing. Finally, the patterns were analyzed by Pearson/Spearman rank correlation, Kyoto Encyclopedia of Genes and Genomes, and Cytoscape 3.7.ResultsFirst, 1,216, 983, 1,606, and 2,459 differentially expressed lncRNAs were identified in CVB3-treated A/J, C57BL/6, BALB/c, and C3H mice with myocarditis, respectively. Among them, 88 lncRNAs were commonly dysregulated in all four models. Quantitative real-time polymerase chain reaction analyses further confirmed that four out of the top six commonly dysregulated lncRNAs were upregulated in all four models. Moreover, the levels of ENSMUST00000188819, ENSMUST00000199139, and ENSMUST00000222401 were significantly elevated in the heart and spleen and correlated with the severity of cardiac inflammatory infiltration. Meanwhile, 923 FM-specific dysregulated lncRNAs were detected, among which the levels of MSTRG.26098.49, MSTRG.31307.11, MSTRG.31357.2, and MSTRG.32881.28 were highly correlated with LVEF.ConclusionExpression of lncRNAs is significantly dysregulated in acute myocarditis, which may play different roles in the progression of AM.</p

DataSheet_4_Expression Profiles and Potential Functions of Long Non-Coding RNAs in the Heart of Mice With Coxsackie B3 Virus-Induced Myocarditis.zip

AimsLong non-coding RNAs (lncRNAs) are critical regulators of viral infection and inflammatory responses. However, the roles of lncRNAs in acute myocarditis (AM), especially fulminant myocarditis (FM), remain unclear.MethodsFM and non-fulminant myocarditis (NFM) were induced by coxsackie B3 virus (CVB3) in different mouse strains. Then, the expression profiles of the lncRNAs in the heart tissues were detected by sequencing. Finally, the patterns were analyzed by Pearson/Spearman rank correlation, Kyoto Encyclopedia of Genes and Genomes, and Cytoscape 3.7.ResultsFirst, 1,216, 983, 1,606, and 2,459 differentially expressed lncRNAs were identified in CVB3-treated A/J, C57BL/6, BALB/c, and C3H mice with myocarditis, respectively. Among them, 88 lncRNAs were commonly dysregulated in all four models. Quantitative real-time polymerase chain reaction analyses further confirmed that four out of the top six commonly dysregulated lncRNAs were upregulated in all four models. Moreover, the levels of ENSMUST00000188819, ENSMUST00000199139, and ENSMUST00000222401 were significantly elevated in the heart and spleen and correlated with the severity of cardiac inflammatory infiltration. Meanwhile, 923 FM-specific dysregulated lncRNAs were detected, among which the levels of MSTRG.26098.49, MSTRG.31307.11, MSTRG.31357.2, and MSTRG.32881.28 were highly correlated with LVEF.ConclusionExpression of lncRNAs is significantly dysregulated in acute myocarditis, which may play different roles in the progression of AM.</p

DataSheet_6_Expression Profiles and Potential Functions of Long Non-Coding RNAs in the Heart of Mice With Coxsackie B3 Virus-Induced Myocarditis.zip

AimsLong non-coding RNAs (lncRNAs) are critical regulators of viral infection and inflammatory responses. However, the roles of lncRNAs in acute myocarditis (AM), especially fulminant myocarditis (FM), remain unclear.MethodsFM and non-fulminant myocarditis (NFM) were induced by coxsackie B3 virus (CVB3) in different mouse strains. Then, the expression profiles of the lncRNAs in the heart tissues were detected by sequencing. Finally, the patterns were analyzed by Pearson/Spearman rank correlation, Kyoto Encyclopedia of Genes and Genomes, and Cytoscape 3.7.ResultsFirst, 1,216, 983, 1,606, and 2,459 differentially expressed lncRNAs were identified in CVB3-treated A/J, C57BL/6, BALB/c, and C3H mice with myocarditis, respectively. Among them, 88 lncRNAs were commonly dysregulated in all four models. Quantitative real-time polymerase chain reaction analyses further confirmed that four out of the top six commonly dysregulated lncRNAs were upregulated in all four models. Moreover, the levels of ENSMUST00000188819, ENSMUST00000199139, and ENSMUST00000222401 were significantly elevated in the heart and spleen and correlated with the severity of cardiac inflammatory infiltration. Meanwhile, 923 FM-specific dysregulated lncRNAs were detected, among which the levels of MSTRG.26098.49, MSTRG.31307.11, MSTRG.31357.2, and MSTRG.32881.28 were highly correlated with LVEF.ConclusionExpression of lncRNAs is significantly dysregulated in acute myocarditis, which may play different roles in the progression of AM.</p

MOESM1 of MiR-30c/PGC-1β protects against diabetic cardiomyopathy via PPARα

Additional file 1: Figure S1. Different expression genes belonging to PPAR family between diabetic hearts and normal ones. Figure S2. High palmitate treatment impaired the insulin signal of NRCMs. Figure S3. The efficacy of siRNAs against PGC-1β. Figure S4. Identification of the primary neonatal rat cardiomyocytes. Figure S5. PGC-1β knockdown relieved high palmitate induced lipotoxicity in vitro. Figure S6. The effects of PGC-1β knockdown on mitochondrial biogenesis and membrane potentials. Figure S7. Overexpression of miR-30c alleviated high palmitate induced lipotoxicity in vitro. Figure S8. The effect of miR-30c on mitochondrial biogenesis and membrane potentials. Figure S9. The effects of rAAV9 mediated miR-30c/anti-miR-30c delivery on plasma lipid profile and blood glucose in vivo. Figure S10. The effects of rAAV9 mediated miR-30c/anti-miR-30c delivery on liver steatosis in vivo. Table S1. The wildtype sequence containing predicted miR-30c binding site of the human PGC-1β 3′ UTR and corresponding mutant sequence. Table S2. Sequences of miR-30c, anti-miR-30c, or miR-random inserted into rAAV expression plasmid. Table S3. Primers of CD36 and PDK4 promotors in ChIP-PCR. Table S4. Primers of rat 12S ribosomal DNA, COI and and 18S ribosomal DNA in real-time PCR. Table S5. Comparison of hemodynamic variables among mice with different treatments