Diagnostic and Predictive Values of Circulating Extracellular Vesicle-Carried microRNAs in Ischemic Heart Disease Patients With Type 2 Diabetes Mellitus

Figures

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  Figure 1. Human sourced plasma-derived EVs were collected and characterized. (A) Representative transmission electron microscopy (TEM) images and the nanoparticle tracking analysis (NTA) of plasma-derived EVs from healthy controls. (B) Representative TEM and NTA of plasma-derived EVs from IHD-DM patients. (C) Representative immunoblot images show enrichment of EV/exosomal markers CD63 and CD81 in plasma-derived EVs. IHD-DM: ischemic heart disease patients with diabetes mellitus; CTR: healthy controls.

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  Figure 2. Cluster analysis of differentially expressed EV-carried miRNAs between IHD-DM and healthy controls. (A) Heatmap of differentially expressed EV-carried miRNAs between IHD-DM patients and healthy controls. (B) Volcano plots of EV-carried miRNAs expression levels in plasma of IHD-DM and healthy controls. x- and y-axes show estimated expression difference measured in log2 (fold change) and the significance of the expression difference measured in -log10 (P-value), respectively. Vertical lines referred to a two-fold difference in expression between the two groups.

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  Figure 3. Validation of differentially expressed EV-carried miRNAs between healthy controls and IHD-DM patients. (A) EV-carried miRNAs including miR-15a-3p, miR-18a-5p, miR-19a-3p, miR-133a-3p, miR-155-5p, and miR-210-3p are differentially expressed between the IHD-DM patients and healthy controls. (B) miRNAs such as miR-20a-5p, miR-26a-5p, miR-30e-5p, miR-92a-2-5p, miR-181a-5p, miR-181b-5p, and miR-301a-3p were not statistically significant between the two groups. *P < 0.05, **P < 0.01, and ***P < 0.001 indicates significance compared with the control group.

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  Figure 4. EV-carried miRNAs as useful biomarkers to distinguish IHD-DM from healthy controls. ROC curve analyses displayed EV-carried miR-15a-3p, miR-18a-5p, miR-19a-3p, miR-133a-3p, miR-155-5p, and miR-210-3p as useful biomarkers to discriminate IHD-DM from healthy controls. P < 0.05 was considered statistically significant. AUC: area under the curve.

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  Figure 5. Schematic summary for the identified EVs-derived miRNA biomarkers for IHD-DM patients.