MicroRNA Signatures in Plasma of Patients With Venous Thrombosis: A Preliminary Report

Venous thromboembolism (VTE) is a frequent and potentially fatal disease, but its pathophysiology is incompletely understood. microRNAs (miR) dysregulate hemostatic proteins and influence thrombotic pathology by posttranscriptional regulation of gene expression. Consensus in defining VTE-related miR clusters and functionally relevant miR has not been reached. We aimed to generate a miR database in patients at high thrombotic risk of VTE and explored their biological functions by seeking information on their messenger RNA targets. By high-throughput screening (Affymetrix miRNA Microarray), we identified 159 miR in venous blood of male patients who had two unprovoked VTE and in age-matched male controls. Of the 159 miR, 41 were significantly higher expressed in patients compared to controls. Six miR (hsa-miR-6798-3p, hsa-miR-6789-5p hsa-miR-4651, hsa-miR-6765-5p, hsa-miR-6816-5p, hsa-miR-4734) were modulated ≥ 5.0-fold higher. Higher expression levels of 4 of these miR (hsa-miR-6789-5p, hsa-miR-4651, hsa-miR-6765-5p, and hsa-miR-6816-5p; primers were unavailable for hsa-miR-6798-3p and hsa-miR-4734) were confirmed by quantitative real-time polymerase chain reaction in 10 independent patients and 10 control samples. Ingenuity Pathway Analysis identified 23 altered miR including hsa-miR-6789-5p, hsa-miR-4651, hsa-miR-6765-5p and hsa-miR-4734 as the main regulators of messenger RNAs involved in the pathology of VTE. Seven messenger RNA targets including thrombomodulin and four targets related to platelet function had a direct relationship to 4 identified miR. We provide evidence of distinct, independently validated miR signatures in patients with VTE and identified a subset of miR as main regulators of messenger RNA involved in disorders related to pathophysiologic processes in venous thrombosis development.