Identification of novel target genes in exaggerated cardiac remodeling following myocardial infarction in diabetes

Figures

• 

  Figure 1. Diabetes increased post-MI cardiac injury. (A) Cardiac function was assessed using echocardiography, with two representative sets of left ventricular M-mode echocardiography images displayed. (B-H) Quantification of EF, FS, LVmass, LVIDd, LVIDs, LV Vol-d, and LV Vol-s was derived from the echocardiographic analysis. (I, J) Analysis of interstitial fibrosis. (K, L) Wheat germ agglutinin (WGA, scale bar=50μm) staining were performed to evaluate the cardiac hypertrophic growth. n = 5/group. EF, ejection fraction; FS, fractional shortening; LVmass, Left Ventricular Mass; LVIDd, Left Ventricular Internal Diastolic Diameter, LVIDs, Left Ventricular Internal Systolic Diameter; LV Vol-d, Left Ventricular Diastolic Volume; LV Vol-s, Left Ventricular Systolic Volume.

• 

  Figure 2. mRNA expression profile in cardiac tissues from MI mice with diabetes. (A) Differential expression of mRNA; (B) Upregulated genes. (C) Downregulated genes. (D) Significantly upregulated pathways. (E) Significantly downregulated pathways. The y-axis represents the GO category, and the x-axis represents the negative log-transformed p-value (-lgP), where a larger -lgP value indicates a smaller p-value.

• 

  Figure 3. Global Signal Transduction Network and Pathway Network. (A) a co-expression network for differentially expressed mRNAs, constructed based on the results of mRNA sequencing. (B) a pathway network derived from KEGG-enriched pathways. The relationships between genes/pathways are represented by edges. And the size of each node indicates the correlation strength.

• 

  Figure 4. Hierarchical cluster reveals the relatedness of differentially expressed LncRNAs. (A) Heatmap showing the relative abundance of significantly altered lncRNAs in the ND+MI and HFD+MI groups. (B) LncRNA-mRNA expression correlation network analysis of core lncRNAs and their correlated mRNAs regulated by post-MI with diabetes. Square nodes represent lncRNAs, while round nodes represent mRNAs. The lines between nodes indicate a correlation, with a solid line representing positive correlation and a dotted line representing a negative correlation. The size of each node represents the correlation strength.

• 

  Figure 5. Verifying the target genes. (A, B) The overlapped target genes of AC165273.2, 2310039LI5Rik, and AC160401.1 are presented using venn diagram and heatmap. (C) The mRNA levels of target genes in the cardiac tissue of STEMI patients with diabetes were analyzed. N=5 independent experiments/group. Data were analyzed by t-test (GraphPad Prism 9.0).

• 

  Figure 6. Both Rapgef5 and Ing1 are involved in proliferation and apoptosis of AC16 cells induced by HG/HL with hypoxia/reoxygenation. (A) CCK8 assay demonstrated that Rapgef5 overexpression and Ing1 knockdown promoted AC16 cells growth and viability. (B, C) Apoptosis in AC16 cells were determined by Annexin V/PI staining. N=5~8 independent experiments/group. Data were analyzed by two-way analysis of variance (GraphPad Prism 9.0).