Transcriptomic profile analysis of the left atrium in spontaneously hypertensive rats in the early stage

Figures

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  FIGURE 1. An overall flow chart of the experimental design. WKY, Wistar-Kyoto; SHR, spontaneously hypertensive rat; ARB, angiotensin receptor blocker; ARNI, angiotensin receptor/neprilysin inhibitor; DEGs, differentially expressed genes; IHC, immunohistochemistry.

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  FIGURE 2. An overview of the transcriptomic landscape profile in the rats’ left atrium. (A) PCA analyse of transcriptome profiles between the four groups: the abscissa and ordinate represent different principal components and their contribution proportions. (B) Heatmap indicating the atlas of dysregulated genes in the four groups: the abscissa represents different groups of rats, the ordinate represents different genes, red represents up-regulated genes, and blue represents down-regulated genes. PCA, principal component analysis; WKY, Wistar-Kyoto; SHR, spontaneously hypertensive rat; ARB, angiotensin receptor blocker; ARNI, angiotensin receptor/neprilysin inhibitor; FPKM, fragments per kilobase of exon per million reads mapped.

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  FIGURE 3. Morphology of the left atrium in different groups. (A) The left atriums were harvested for H&E and Masson’s trichrome. (B) Quantitative analyses of areal density (IOD/area) in Masson’s trichrome in four groups. (C) Quantitative analyses of the area ratio of collagen fibers in Masson’s trichrome in four groups. H&E, hematoxylin-eosin; WKY, Wistar-Kyoto; SHR, spontaneously hypertensive rat; ARB, angiotensin receptor blocker; ARNI, angiotensin receptor/neprilysin inhibitor; IOD, integral optical density; ns, no significance. *: p ≤ 0.05.

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  FIGURE 4. GO and KEGG pathway analysis of DEGs between SHR and WKY rat left atrium. (A) Histogram of the numbers of DEGs: the abscissa represents the direction of gene change, the ordinate represents the number of genes, red represents up-regulation, blue represents down-regulation; (B) volcano Plot: X-axis represents the fold change of log2, Y-axis represents −log10 (p-value), red represents up-regulated genes, blue represents down-regulated genes, and gray represents insignificant genes; (C) heatmap: X-axis represents different groups of rats, Y-axis represents different genes, red represents up-regulated genes, blue represents down-regulated genes. (D,E) Ten GO enriched terms in the upregulated (D) and downregulated (E) DEGs, were analyzed for biological process (BP), cellular component (CC), and molecular function (MF). The X-axis shows different pathways, and the Y-axis shows enrichment scores, BP in green, CC in orange, and MF in blue. (F,G) 10 KEGG pathways were identified in the downregulated (F) and upregulated (G) DEGs. The X-axis represents the enrichment ratio, the Y-axis represents the different pathways enriched, the size of the dots represents the number of genes enriched to…

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  FIGURE 5. Network analysis of DEGs and enriched pathways between THE WKY and SHR groups. (A) KDA analysis identified 15 key driver genes in the DEGs between SHR and WKY rat atria: Key driver genes are shown in red, initial genes are shown in blue, and extended genes are shown in gray. (B) Heatmap of the 15 key driver genes. (C) Network analysis between key driver genes and enriched KEGG pathways: Dots represent genes, squares represent KEGG pathways, and lines between genes and squares indicate that the gene can be enriched into the corresponding pathway. (D) The top 20 hub genes were selected by the cytoHubba app in Cytoscape 3.8.2 software. The node color changed gradually from yellow to red in ascending order according to the score of hub genes. (E) GO and enrichment network of the top 20 hub genes between SHR and WKY rat atrium. (F) The enrichment network of top 20 hub genes was identified in the rat atrium. Nodes represent functions enriched for an annotated ontology term and node size indicates the number of genes that fall into that term. KDA, key driver gene analysis; WKY, Wistar-Kyoto; SHR, spontaneously hypertensive rat; KEGG, kyoto encyclopedia of genes and genomes; BP,…

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  FIGURE 6. GSEA between the ARB-treated group and the SHR (A), sacubitril/valsartan-treated group and the SHR (B), and the ARB-treated and sacubitril/valsartan-treated groups (C) TCA, tricarboxylic acid; AMPK, AMP-activated protein kinase; PPAR, peroxisome proliferator-activated receptor; ECM, extracellular matrix; MAPK, mitogen-activated protein kinase.

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  FIGURE 7. (A) Immunohistochemical analysis of the left atrium in different groups: the TGF-beta-positive cells manifested as buffy, and the nucleus was stained blue. (B) Expression levels of TGF beta in SHR and WKY: the X-axis represents different groups, and the Y-axis represents FPKM. (C) Mean density of Immunofluorescence staining: the X-axis represents different groups, and the Y-axis represents the mean density. WKY, Wistar-Kyoto; SHR, spontaneously hypertensive rat; FPKM, fragments per kilobase of exon per million reads mapped.