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

OBJECTIVE Cardiovascular disease (CVD) accounts for most deaths in patients with type 1 diabetes (T1D); however, the determinants of plaque composition are unknown. MicroRNAs (miRNAs) regulate gene expression, participate in the development of atherosclerosis and represent promising CVD biomarkers. This study analyzed the circulating miRNA expression profile in T1D with carotid either calcified (CCP) or fibrous (CFP) plaque. RESEARCH DESIGN AND METHODS Circulating small non-coding RNA were sequenced and quantified using NGS and bioinformatic analysis in an exploratory set of 26 T1D with CCP and in 25 with CFP. Then, in a validation set of 40 CCP, 40 CFP and 24 controls T1D, selected miRNAs expression was measured by digital droplet PCR. Putative gene targets enriched for pathways implicated in atherosclerosis/vascular calcification/diabetes were analyzed. Patient’s main clinical characteristics were also recorded. RESULTS miR-503-5p, let-7d-5p, miR-106b-3p, miR-93-5p were significantly up-regulated, while miR-10a-5p downregulated in CCP patients compared to CFP (all FC>±1.5, p CONCLUSIONS These findings characterize miRNAs and their signature in the regulatory network of carotid plaque phenotype, in T1D, providing new insights into plaque pathophysiology, and possibly novel biomarkers of plaque composition.