Aging-dependent expression of vascular endothelial growth factor receptor-1 is associated with T-cell immune senescence in carotid atherosclerosis

Figures

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  Figure 1. Flow chart of study

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  Figure 2. Identification and foundational of differentially expressed aging-related genes. (a) Fresh human carotid plaques were obtained from carotid endarterectomy surgery, and one intact plaque was sectioned into early stage plaque and advanced-stage plaque. (b) Typical micrographs of β-gal immunohistochemical staining, and macroscopic view of the cross sections at lower left of microscopic views. (c) Histogram showed the quantitative results of immunohistochemical staining. β-gal expression was significantly increased in the advanced-stage plaque group (**P < 0.01). (d) The Volcano map showed differentially expressed genes in early and advanced plaques. (e) Differential aging-related genes were screened by Venn diagram. (f) Heat maps showed the expression of aging-related genes in early and advanced plaques. (g) The box diagram showed the expression of aging-related genes in early and advanced plaques. (h) Bubble plots showed the results of functional enrichment. (i) The table showed the specific contents of Gene Ontology and KEGG results (P adjust < 0.05)

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  Figure 3. Build models to screen key aging-related genes. (a) Residual comparison between random forest (RF) and support vector machine (SVM) models. (b) Receiver operating characteristic (ROC) curves of RF and SVM models showed diagnostic efficiency. (c) Results of random forest tree construction model. (d) Sequencing the importance of differentially aging-related genes. (e-i) ROC diagnostic curves of 5 key genes (PLCG2, GRN, PRKCD, LMNB1, Vascular endothelial growth factor receptor-1)

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  Figure 4. Identify immune cell subpopulations and key gene expression patterns. (a) Ten cell subpopulations were identified by Seurat package. (b) Expression of marker genes in cell subsets. (c) Ten cell subpopulations were named according to marker genes. (d-f) Expression patterns of key genes in cell subsets (Vascular endothelial growth factor receptor-1, GRN, PLCG2)

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  Figure 5. Cell proportion, communication, and validation of Trail and Vascular endothelial growth factor receptor-1 (VEFGR1) in carotid plaques. (a) The proportion of different types of cells in early and advanced plaques. (b) The role of VEGF signaling pathway in cell interaction. (c) The interaction between various ligand receptors and cells. (d) Interactive signaling pathways received by various cell subpopulations. (e) Interactive signaling pathways emitted by various cell subpopulations. (f) Typical micrographs of Trail and VEFGR1 immunohistochemical staining, and macroscopic view of the cross sections at lower left of microscopic views. (g) Histograms showed the quantitative results of immunohistochemical staining. Trail expression was significantly increased in the early-stage plaque group. VEFGR1 expression was significantly increased in the advanced-stage plaque group. **P < 0.01, ***P < 0.001

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  Figure 6. Functional enrichment of differential genes in memory T-cells and Schema diagram of mechanism. (a) The dot plot showed the Gene Ontology and KEGG enrichment results. (b) Gene set enrichment analysis results showed that the Interleukin-18 signaling pathway was inhibited (FDR < 0.25, p.adj < 0.05). (c) Schema diagram of mechanism