Role of mitochondrial metabolic disorder and immune infiltration in diabetic cardiomyopathy: new insights from bioinformatics analysis

Figures

• 

  Fig. 1. Flowchart of the multistep screening strategy on bioinformatics data

• 

  Fig. 2. DEGs in DCM and results of GSEA analysis. a–c Volcano plot of DEGs in GSE4745, GSE5606, GSE6880; d–f Clustered heatmap of DEGs in GSE4745, GSE5606, GSE6880; g–i GSEA profiles depicting the 7 significant GSEA sets in lipid metabolism; j 3 significant GSEA sets in oxidative stress; k, l 4 significant GSEA sets in immunity; m, n 10 significant GSEA sets in collagen biosynthesis

• 

  Fig. 3. GO and KEGG enrichment analyses of DEGs from GSE4745, GSE5606 and GSE6880. a, b The enriched GO terms of DEGs in GSE4745; c, d The enriched GO terms of DEGs in GSE5606; e, f The enriched GO terms of DEGs in GSE6880; g, h KEGG pathway enrichment results in GSE4745; i, j KEGG pathway enrichment results in GSE5606; k, l KEGG pathway enrichment results in GSE6880. BP biological process, CC cellular component, MF molecular function

• 

  Fig. 4. MitoDEGs in DCM; PPI network analysis and hub MitoDEGs identification. a, b Venn diagrams showed the number of upregulated a and downregulated b DEGs that overlap between GSE4745, GSE5606, GSE6880, MitoCarta3.0; c Clustered heatmap of DEGs both in GSE4745 and MitoCarta3.0; d Clustered heatmap of DEGs both in GSE5606 and MitoCarta3.0; e Clustered heatmap of DEGs both in GSE6880 and MitoCarta3.0; f PPI network of MitoDEGs; g A key cluster with 9 genes was further chosen as hub genes by MCODE; h Top 10 hub genes explored by CytoHubba

• 

  Fig. 5. Relationship between hub MitoDEGs and DCM/HF; Hub MitoDEGs-TFs-miRNAs regulatory network. a, b Hub MitoDEGs related to DCM and HF diseases based on the CTD database; c TF–hub MitoDEGs regulatory network: the red squares represent hub MitoDEGs, and the yellow dots represent transcription factors; d miRNA–hub MitoDEGs regulatory network: the red squares represent hub MitoDEGs, and the purple dots represent miRNA

• 

  Fig. 6. Infiltration of immune cell types compared between the DCM and CON. a The violin plot of the immune cell proportions; b Stacked bar chart of the immune cell; c Heatmap of the proportions of 36 immune cell types; d The correlation matrix of immune cell proportions

• 

  Fig. 7. Relationship between MitoDEGs/hub MitoDEGs and immune cells. a, b The correlation between upregulated a and downregulated b DEGs and immune cells; c The correlation between hub MitoDEGs and immune cells

• 

  Fig. 8. Confirmation of hub MitoDEGs expression and association with cardiac function in DCM rats. a–j General biological and echocardiography features of DCM rats; k Hub MitoDEGs mRNA expression of CON and DCM rats; l, m Protein levels of Pdk4, Hmgcs2, Decr1 and Ivd by western blotting, and quantitative analysis in cardiac tissues; n Immunostaining of Pdk4, Hmgcs2, Decr1 and Ivd protein expression. o Correlations between Pdk4, Hmgcs2, Decr1, Ivd mRNA levels and cardiac functional parameters in CON and DCM rats, including: EF%, FS%, LVIDs(mm). Mean ± SD, n = 4 rats per group. *p < 0.05, **p < 0.01, ***p < 0.001 and ****p < 0.0001 vs. control group. ns no significance