Novel Targets Regulating the Role of Endothelial Cells and Angiogenesis after Infarction: A RNA Sequencing Analysis

Figures

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  Figure 1. Endothelial cell proliferation, apoptosis-related BPs, (A) and angiogenesis-related BPs (B) overrepresented at each time point after coronary occlusion. Myocardial infarction groups are in the columns, while the rows represent the different BPs. The size of the circle indicates the number of overexpressed genes, whereas the colors ranging from red to blue represent adjusted p-value, as shown in the legend. The red circles in the figure indicate lower p-values, while the blue represent higher p-values. Abbreviation. BP: biological process.

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  Figure 2. Genes involved in endothelial cell proliferation regulation in the context of myocardial infarction. The Venn diagram represents GO included in the BPs underlying the regulation of endothelial cell proliferation (GO: 0001936), positive regulation of endothelial cell proliferation (GO: 0001938), and negative regulation of endothelial cell proliferation (GO: 0001937). According to the Venn diagram, 18 genes were implicated in the positive and 9 in the negative regulation of angiogenesis. Heatmaps of the Log2-fold change of the genes included in the cross-section groups are represented at each time point after ischemia onset. Myocardial infarction groups are in the columns and genes in the rows. Gene intensities were log2-transformed and are displayed in colors ranging from red to green, as shown in the key. The red squares in the figure represent high-expression genes, while green squares represent low-expression genes. The rows are clustered using correlation distance and average linkage. Abbreviations. BP: biological process. GO: gene ontology.

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  Figure 3. Endothelial cell apoptosis and extrinsic and intrinsic apoptotic signaling pathway-related BPs differentially expressed at each time point after myocardial infarction. The Venn diagram represents the GO included in the BPs underlying the endothelial cell apoptotic process (GO: 0072577), intrinsic apoptotic signaling pathway (GO: 0097193), and extrinsic apoptotic signaling pathway (GO: 0097191). According to the Venn diagram, 14 genes implicated in endothelial cell apoptosis belong to the extrinsic signaling pathway, 2 to the intrinsic, and 3 to both the intrinsic and extrinsic signaling pathways. Heatmaps of the log2-fold change of the genes included in the cross-section groups are represented at each time point after ischemia onset. Myocardial infarction groups are in the columns and genes in the rows. Gene intensities were log2-transformed and are displayed in colors ranging from red to green, as shown in the key. The red squares in the figure represent high-expression genes, while the green squares represent low-expression genes. The rows are clustered using correlation distance and average linkage. Abbreviations. BP: biological process. GO: gene ontology.

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  Figure 4. Genes related to angiogenesis regulation in a myocardial infarction scenario. The Venn diagram represents the GO included in the BPs underlying the regulation of angiogenesis (GO: 0045765), positive regulation of angiogenesis (GO: 0045766), and negative regulation of angiogenesis (GO: 0016525). According to the Venn diagram, 68 genes were implicated in the positive and 29 in the negative regulation of angiogenesis. Heatmaps of the log2-fold change of the genes included in the cross-section groups are represented at each time point after ischemia onset. Myocardial infarction groups are in the columns and genes in the rows. Gene intensities were log2-transformed and are displayed in colors ranging from red to green, as shown in the key. The red squares in the figure represent high-expression genes, while the green squares represent low-expression genes. The rows are clustered using correlation distance and average linkage. Abbreviations. BP: biological process. GO: gene ontology.

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  Figure 5. Heatmap of the log2-fold change of pro-angiogenic (A) and anti-angiogenic (B) genes at different time points after coronary reperfusion. Columns show myocardial infarction groups and the different genes encoding angiogenesis-related genes are in the rows. Gene intensities were log2-transformed and are displayed as colors ranging from red to green, as shown in the key. The red squares in the figure represent high-expression genes, while the green squares represent low-expression genes. Both the rows and columns are clustered using correlation distance and average linkage.

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  Figure 6. Central illustration. The transcriptomic level of the genes participating in EC apoptosis (via the extrinsic and intrinsic pathways) increases up to day 3 after ischemia onset, whereas EC proliferation occurs from day 3 onwards. In terms of angiogenesis modulation, the BPs implicated in new vessel formation are overrepresented as early as ischemia onset, while the mechanisms aiming at inhibiting this process are detected from day 3 onwards. Image created with BioRender.com, accessed on 13 September 2023.