Journal
EBIOMEDICINE
Volume 26, Issue -, Pages 175-186Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ebiom.2017.11.022
Keywords
Venous thrombosis; miRNA; Tissue factor; Antithrombotic therapy; Coagulation
Funding
- Defence Research and Development Organization [SL-10/DIP-255]
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Venous thromboembolism(VTE), the third leading cardiovascular complication, requires more understanding at molecular levels. Here, we have identified miR-145 as a key molecule for regulating thrombus formation in venous thrombosis (VT) employing network based bioinformatics approach and in vivo experiments. Levels of miR-145 showed an inverse correlation with thrombus load determined by coagulation variables. MiRNA target prediction tools and in vitro study identified tissue factor (TF) as a target gene for miR-145. The restoration of miR-145 levels in thrombotic animals via in vivo miR-145 mimic delivery resulted in decreased TF level and activity, accompanied by reduced thrombogenesis. MiR-145 levels were also reduced in VT patients and correlated with increased TF levels in patients, thereby, confirming our preclinical findings. Our study identifies a previously undescribed role of miRNA in VT by regulating TF expression. Therefore, restoration of miR-145 levels may serve as a promising therapeutic strategy for management of VT. (C) 2017 Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license.
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