Biomarker value of plasma endothelial microvesicle-derived circRNA 0006222 in vascular ageing and carotid atherosclerosis

Figures

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  Figure 1. Heatmap illustrating the top ten differentially expressed circRNAs (both up- and down-regulated) in EMVs from control, VA and CAS participants. (A) Distribution and diversity of circulating EMV-circRNAs analyzed by high-throughput transcriptome sequencing. (B) Scatter plot with axes showing the mean normalized signal values (log2 scaled) of the sample groups. Rows represent circRNAs and columns represent samples. Red and green denote upregulation and downregulation, respectively. (C) EMVs-circ_0006222 levels in the control, VA and CAS groups, as assessed via qRT-PCR (control vs. VA: *p = 0.04; control vs. CAS: **p = 0.002; VA vs. CAS: *p = 0.045).

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  Figure 2. Plasma EMVs-circ_0006222 levels in various age groups and in both control, VA and CAS participants. (A) Plasma EMVs-circ_0006222 levels in young, middle-aged, and aged participants (***p < 0.001). (B) Spearman correlation analysis between plasma EMVs-circ_0006222 levels and age, demonstrating a significant negative correlation (r = −0.562, p < 0.001). (C) Comparison of EMVs-circ_0006222 levels across different age groups among the control, VA and CAS participants (control group: young vs. middle-aged participants, no significant difference (ns); middle-aged vs. aged participants, ns; young vs. aged participants, *p = 0.02; VA group: young vs. middle-aged participants, ns; middle-aged vs. aged participants, *p = 0.041; young vs. aged participants, ***p < 0.001; CAS group: young vs. middle-aged participants, ***p < 0.001; middle-aged vs. aged participants, *p = 0.045; young vs. aged participants, ***p < 0.001).

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  Figure 3. Plasma EMVs-circ_000622 levels in control, VA and CAS participants and different severity of CAS. (A) Comparison of plasma EMVs-circ_0006222 levels among control, VA and CAS participants (control vs. VA: *p = 0.049; VA vs. CAS: ***p < 0.001; control vs. CAS: ***p < 0.001). (B) Plasma EMVs-circ_0006222 levels in control, VA and CAS participants across different age groups (young group: control vs. VA, ns; VA vs. CSA, ns; control vs. CAS, **p = 0.003; middle-aged group: control vs. VA, *p = 0.04; VA vs. CSA, ***p < 0.001; control vs. CAS, ***p < 0.001; aged group: control vs. VA, *p = 0.02; VA vs. CSA, ***p < 0.001; control vs. CAS, ***p < 0.001). (C) Plasma EMVs-circ_0006222 levels in different CAS severity groups (mild vs. moderate: ***p < 0.001; mild vs. severe: ***p < 0.001; moderate vs. severe: **p = 0.009).

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  Figure 4. ROC curves for discriminating VA and CAS by EMVs-circ_0006222. (A,B) Plasma EMVs-circ_0006222 exhibited relatively high diagnostic accuracy for VA and CAS (VA: AUC = 0.628; specificity, 54.3%; sensitivity, 76.8%; CAS: AUC = 0.773; specificity, 73.2%; sensitivity, 75.8%).