Circulating small non-coding RNA profiling as potential biomarkers of atherosclerotic plaque composition in Type 1 diabetes

Cardiovascular disease (CVD) accounts for the majority of deaths in patients with type 1 diabetes (T1D); however, the determinants of plaque composition are unknown in this population. MicroRNAs (miRNAs), the most abundant class of circulating small non-coding RNA (sncRNAs) regulating gene expression, participate in the development of atherosclerosis and represent promising biomarkers of CVD. This study analyzed the circulating miRNA expression profile in T1D with carotid calcified and fibrous plaque. We identified four upregulated (miR-503-5p, let-7d-5p, miR-106b-3p, miR-93-5p) and one downregulated (miR-10a-5p) miRNAs in patients with calcified plaque(s) compared to those with fibrous plaque(s). ROC curve analysis demonstrated that miR-503-5p and miR-10a-5p discriminate with good performance in the different plaque compositions. miR-503-3p inversely and miR-10a-5p directly correlate with LDL cholesterol concentrations. Pathway enrichment analysis of putative gene targets of selected miRNAs revealed involvement in apoptotic and inflammatory processes regulation, osteogenic differentiation, and vascular calcification. These findings comprehensively characterize miRNAs and their signature in the regulatory network, leading to different plaque compositions in T1D. These results could have important clinical implications for developing novel therapeutic strategies to prevent CVD in diabetes. Overall design: miRNA profile in plasma from type 1 diabetes and atherosclerotic plaque