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. 2022 Jun 13:2022:2923291.
doi: 10.1155/2022/2923291. eCollection 2022.

UTP14A, DKC1, DDX10, PinX1, and ESF1 Modulate Cardiac Angiogenesis Leading to Obesity-Induced Cardiac Injury

Xiaoyu Pan  1   2 , Shuchun Chen  1   2 , Xing Chen  1   2 , Qingjuan Ren  1   2 , Lin Yue  1   2 , Shu Niu  1   2 , Zelin Li  1   2 , Ruiyi Zhu  1   2 , Xiaoyi Chen  2 , Zhuoya Jia  1   2 , Ruoxi Zhen  1   2 , Jiangli Ban  2
Affiliations

UTP14A, DKC1, DDX10, PinX1, and ESF1 Modulate Cardiac Angiogenesis Leading to Obesity-Induced Cardiac Injury

Xiaoyu Pan et al. J Diabetes Res. .

Abstract

Background: This study is aimed at exploring the key genes and the possible mechanism of heart damage caused by obesity.

Methods: We analyzed the GSE98226 dataset. Firstly, differentially expressed genes (DEGs) were identified in heart tissues of obese and normal mice. Then, we analyzed DEGs using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Thirdly, we constructed a protein-protein interaction (PPI) network and key modules and searched hub genes. Finally, we observed the pathological changes associated with obesity through histopathology.

Results: A total of 763 DEGs were discovered, including 629 upregulated and 134 downregulated genes. GO enrichment analysis showed that these DEGs were mainly related to the regulation of transcription, DNA-templated, nucleic acid binding, and metal ion binding. KEGG pathway analysis revealed that the DEGs were enriched in long-term depression, gap junction, and sphingolipid signaling pathways. Finally, we identified UTP14A, DKC1, DDX10, PinX1, and ESF1 as the hub genes. Histopathologic analysis showed that obesity increased the number of collagen fibers and decreased the number of microvessels and proliferation of the endothelium and increased endothelial cell damage which further leads to dysfunction of cardiac microcirculation.

Conclusion: UTP14A, DKC1, DDX10, PinX1, and ESF1 have been identified as hub genes in obesity-induced pathological changes in the heart and may be involved in obesity-induced cardiac injury by affecting cardiac microcirculatory function.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Screening and visualization of DEGs. (a) Experimental workflow. The hearts of NCD and HFD mice were harvested for DEGs analysis and pathological examination (n = 3). (b) The volcano plots of DEGs. The screening criteria for DEGs were adjusted P value < 0.01 and |log2foldchange(FC)| ≥ 2. (c) The heatmaps of DEGs. Top 50 DEGs between NCD and HFD. Red: greater expression; blue: less expression; DEGs: differentially expressed genes; NCD: normal chow diet; HFD: high-fat diet; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; PPI: protein-protein interaction.
Figure 2
Figure 2
GO terms and KEGG pathway enrichment analysis. The x-axis represents the fold enrichment of each functional group gene. The y-axis represents the different functional groups. The size of the dots indicates the number of genes contained in different functional groups, and the color of the dots reflects the different range of −log10(P value). The larger the number of genes, the larger the dot. The gradient from green to red represents a change in P value from large to small. GO analysis divided DEGs into three functional groups: BP (a), CC (b), and MC (c). (d) Top 10 KEGG pathway enrichment analysis of DEGs. GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; BP: biological processes; CC: cell composition; MF: molecular function; DEGs: differentially expressed genes.
Figure 3
Figure 3
Results of PPI network analysis of DEGs. The circles represent genes; the lines represent the PPI between genes, and the images within the circles represent protein structures. The line color represents the PPI evidence level. PPI: protein-protein interaction; DEGs: differentially expressed genes.
Figure 4
Figure 4
The protein-protein interaction module constructed based on the DEGs (a–c). The size of the circle and the thickness of the line represent the degree of importance; the larger the circle and the thicker the line, the more important it is. The color represents the degree value. Orange means the smallest degree value, while blue means the largest degree value. (d) Venn diagram of common hub genes based on three methods. DEGs: differentially expressed genes; DMNC: Density of Maximum Neighborhood Component; MCC: Maximal Clique Centrality; MNC: Maximum Neighborhood Component.
Figure 5
Figure 5
Effect of high-fat diet on mice. (a) Comparison of NCD and HFD mice. (b) Effect of high-fat diet on body weight of mice (n = 3). (c) A representative macroscopic image of the heart. (d) Comparison of heart weights between the two groups of mice (n = 3). Data were processed using independent samples t-test. ∗∗ represents P < 0.01. NCD: normal chow diet; HFD: high-fat diet.
Figure 6
Figure 6
HE and Masson staining of rat myocardial tissue in each group (200x). HE staining of rat myocardial tissue in each group (a, b). Masson staining of rat myocardial tissue in each group (b, c). The left side of the graph represents the normal group, and the right side represents the high-fat group.
Figure 7
Figure 7
Comparison of cardiac angiogenesis, endothelial cell proliferation, and injury between NCD-heart and HFD-heart. (a) Immunofluorescent staining of Ki67 and CD31 to detect proliferative endothelial cells in NCD and HFD hearts; (b) CD34 immunofluorescence staining to determine the number of cardiac microvessels. (c) VWF immunofluorescence staining to determine the proportion of endothelial cell damage. (d) Comparison of CD34-positive cells per HPF between NCD and HFD hearts (&P > 0.05, n = 3). (e) Comparison of vWF-positive cells per HPF between NCD and HFD hearts (&P > 0.05, n = 3). (f) The comparison of the percentage of Ki67-positive cells between NCD and HFD hearts (&P > 0.05, n = 3). NCD: normal chow diet; HFD: high-fat diet; HPF: high-power field.
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