Differential expression of plasma miRNAs in patients with unprovoked venous thromboembolism and healthy control individuals

Background: Venous thromboembolism (VTE) remains the third most common cardiovascular disease with a vague pathogenesis. Circulating miRNAs are small regulatory RNAs found in plasma, serum and other body fluids in an apparently stable form. Although circulating miRNAs, a novel family of regulatory molecules, emerge as a promising class of biomarkers in many cardiovascular diseases and malignancies, knowledge on plasma miRNA levels in VTE remains sparse. Aims: The present work was conducted as a pilot study in order to estimate the plasma levels of miRNAs in patients with unprovoked VTE and to assess miRNAs as potential novel biomarkers of VTE. Methods: Twenty patients with a history of unprovoked VTE 1-5 years prior to inclusion in the study and twenty age-and sex-matched healthy control participants were enrolled in a case-control study (Tromso IV). Plasma levels of 742 miRNAs were assessed after RNA extraction and reverse transcription. Profiling of miRNA was conducted on the Universal RT microRNA PCR Human panels I and II (Exiqon, Denmark). For normalization of the data, the average of the assays detected in all samples (n = 40 samples) was applied. Results: Ninety-seven miRNAs were detected throughout all samples. Of these, miR-10b-5p, -320a, -320b, -424-5p, and -423-5p were upregulated, whereas miR-103a-3p, -191-5p, -301a-3p, and 199b-3p were downregulated in plasmas of VTE patients versus controls (P <= 0.05). These miRNAs were confined to the extracellular vesicles-depleted plasma fraction, and yielded clear clustering distinguishing samples from the VTE and control groups. Conclusions: The results of this pilot study indicate that plasma miRNAs profiling can provide novel biomarkers of unprovoked VTE. (C) 2015 Elsevier Ltd. All rights reserved.