MicroRNA Signatures in Plasma of Patients With Venous Thrombosis: A Preliminary Report
| Autor: | Jessica Gabler, Oskar Steinbrecher, Marietta Kollars, José Basílio, Paul A. Kyrle, Sabine Eichinger |
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| Rok vydání: | 2021 |
| Předmět: |
Adult
Male Gene Expression 030204 cardiovascular system & hematology Bioinformatics Thrombomodulin law.invention Plasma 03 medical and health sciences 0302 clinical medicine law microRNA medicine Humans Platelet 030212 general & internal medicine Polymerase chain reaction Aged Venous Thrombosis Regulation of gene expression Messenger RNA business.industry Gene Expression Profiling General Medicine Middle Aged medicine.disease Pathophysiology body regions MicroRNAs Venous thrombosis embryonic structures business |
| Zdroj: | The American Journal of the Medical Sciences. 361:509-516 |
| ISSN: | 0002-9629 |
| DOI: | 10.1016/j.amjms.2020.12.002 |
| Popis: | Background 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. Methods 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. Results 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. Conclusions 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. |
| Databáze: | OpenAIRE |
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