Deciphering the Role of miR-200c-3p in Type 1 Diabetes (Subclinical Cardiovascular Disease) and Its Correlation with Inflammation and Vascular Health

Figures

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  Figure 1. Comparison of miR-200c-3p expression between HC and T1DM patients in PBMCs. Data are represented as mean ± SEM and analyzed by unpaired t-tests. ** p < 0.01.

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  Figure 2. (A) Correlation between miR-200c-3p in PBMCs and HbA1c (r2 = 0.314, p = 0.013) as a parameter to portray the glycemic control across study groups, (B) correlation between miR-200c-3p in PMBC and IL7 (r2 = 0.23 p = 0.038), (C) logVEGFC (r2 = 0.263, p = 0.025), (D) sVCAM-1 (r2 = 0.352, p = 0.007), across study groups in the plasma. Statistical analysis was carried out using linear regression analysis. IL: interleukin; VEGFC: vascular endothelial growth factor C; sVCAM-1: circulating vascular cell adhesion molecule 1.

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  Figure 3. Correlation between miR-200c-3p expression in PBMCs and vascular health in type 1 diabetes and healthy controls combined. (A) miR-200c-3p and CD45dimCD34+VEGFR-2+ (B) miR-200c-3p and CD45dimCD34+CD133+; (C) miR-200c-3p and logPACs. Statistical analysis was carried out using linear regression analysis. CD: cluster of differentiation; PAC: proangiogenic cells.

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  Figure 4. (A) Receiver Operating Characteristic Curve (ROC) for miR-200c-3p in type 1 diabetes and healthy controls; (B) ROC curve of HbA1c indicating downregulation of miR-200c-3p expression.

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  Figure 5. Ingenuity Pathway Analysis (IPA) prediction network of miR-200c-3p using our data and its mRNA targets, supporting its involvement in cardiovascular disease. Three pathways were considered relevant in this study: the PI3K-Akt signaling pathway, the Hippo signaling pathway, and the VEGF signaling pathway. The green color denoted decreased measurement, and the orange color denoted upregulation or predicted activation. The lines colored in orange represented stimulation, blue inhibition and grey effect not predicted. Solid lines represented a direct relationship, whereas dashed, interrupted ones represented an indirect relationship. Genes outlined with blue are involved in VEGF signaling, while ones outlined in dim gray are involved in PI3K/Akt signaling pathways. EIF2S1: Eukaryotic Translation Initiation Factor 2 Subunit α; IKBKβ: Inhibitor of Nuclear Factor Kappa B Kinase Subunit β; JUN: Jun Proto-Oncogene, AP-1 Transcription Factor Subunit; KDR: kinase insert domain receptor (VEGFR-2); MAP3K5: Mitogen-Activated Protein Kinase Kinase Kinase 5; PIK3CA: Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit α; PLCG1: Phospholipase C Gamma 1; PPP2CA: Protein Phosphatase 2…