title: Differential expression of plasma miRNAs in patients with unprovoked venous thromboembolism and healthy control individuals.
abstract: 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.
  
  
  OBJECTIVE
  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 (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.
  
  
  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.
authors.affiliation: K. G. Jebsen - Thrombosis Research and Expertise Center (TREC), Department of Clinical Medicine, UiT - The Arctic University of Norway, Tromsø, Norway; Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway. Electronic address: irina.starikova@uit.no.
authors.forename: Irina
authors.initials: I
authors.lastname: Starikova
authors.affiliation: K. G. Jebsen - Thrombosis Research and Expertise Center (TREC), Department of Clinical Medicine, UiT - The Arctic University of Norway, Tromsø, Norway.
authors.forename: Simin
authors.initials: S
authors.lastname: Jamaly
authors.affiliation: Exiqon A/S, Copenhagen, Denmark.
authors.forename: Antonio
authors.initials: A
authors.lastname: Sorrentino
authors.affiliation: Exiqon A/S, Copenhagen, Denmark.
authors.forename: Thorarinn
authors.initials: T
authors.lastname: Blondal
authors.affiliation: K. G. Jebsen - Thrombosis Research and Expertise Center (TREC), Department of Clinical Medicine, UiT - The Arctic University of Norway, Tromsø, Norway.
authors.forename: Nadezhda
authors.initials: N
authors.lastname: Latysheva
authors.affiliation: Section for Medical Biochemistry, Department of Laboratory Medicine, University Hospital of Northern Norway, N-9037, Tromsø, Norway.
authors.forename: Mikhail
authors.initials: M
authors.lastname: Sovershaev
authors.affiliation: K. G. Jebsen - Thrombosis Research and Expertise Center (TREC), Department of Clinical Medicine, UiT - The Arctic University of Norway, Tromsø, Norway; Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway.
authors.forename: John-Bjarne
authors.initials: JB
authors.lastname: Hansen
mesh_terms: D015415:Biomarkers / Q000097:blood; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D012016:Reference Values; D012042:Registries; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D054556:Venous Thromboembolism / Q000097:blood* / Q000235:genetics*
chemical_list: D015415:Biomarkers; D035683:MicroRNAs
keywords: biomarker; extracellular vesicles; microRNA; plasma; venous thromboembolism