MicroRNA as Circulating Biomarkers of Diabetic Cardiovascular Disease
The extracellular miRNAs in human serum and plasma are known to be relatively stable, reproducible and consistent, allowing them to be of potential value as biomarkers, and the interest toward the use of miRNAs in this area is growing. The role of miRNAs as biomarkers in cardiovascular disease is reviewed elsewhere (Creemers et al. 2012). Additionally, circulating levels of several miRNAs are also modified by diabetes (reviewed in (Shantikumar et al. 2012; Rawal et al. 2014)). Zampetaki et al. described the first plasma microRNA signature in patients with T2DM in a large population cohort. They found five microRNAs (miR-15a, miR-126, miR- 320, miR-223, miR-28-3p) to be deregulated in patients with diabetes (Zampetaki et al. 2010). There has been much less study of circulating miRNAs in the specific context of diabetic vascular disease. We found that plasma levels of miR-50, miR- 15a and miR-16 were increased in diabetic patients with CLI. The latter two miRNAs correlate with adverse events during 12 months follow-up in T2D patients who underwent PTA to correct CLI (Spinetti et al. 2013b). Another study looking at serum miRNA expression in T2DM patients, with and without vascular complications, found differential expression in patients with microvascular or macrovascular disease. Specifically, they found that miR-31 was significantly upregulated in T2DM patients with microvascular complications (Sebastiani et al. 2013).
These preliminary findings must be confirmed in larger patient populations, including subjects from different ethnic backgrounds and with various comorbidities. Differences in patient characteristics could alter several processes which determine circulating miRNA values. These processes could include miRNA transcription, maturation, release from cells to the circulation, uptake from the circulation by other cells and excretion. Moreover, the data above leave several questions open regarding circulating miRNAs, including the cellular sources, the stimuli and the mechanisms permitting their extracellular release, their form of transportation and their putative function as local or at-distance communicators (Fichtlscherer et al. 2011).