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

Abstract

BackgroundVenous 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. AimsThe 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. MethodsTwenty 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 (Tromsø 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. ResultsNinety-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. ConclusionsThe results of this pilot study indicate that plasma miRNAs profiling can provide novel biomarkers of unprovoked VTE.