miR-4485-5p in large extracellular vesicles as a new potent biomarker for diagnosis of deep vein thrombosis

Deep vein thrombosis （DVT） is a pathological condition where blood clots form in the veins deeper than the fascia, sometimes leading to serious complications such as pulmonary embolism. DVT is a significant complication of cancer; given the situation where the frequency of cancer is predicted to increase, early diagnosis and intervention of DVT are crucial. Current diagnostic methods, such as blood D-dimer test and ultrasonography of the lower limbs, have limitations in terms of specificity and sensitivity. <br>  In this study, we focused on large extracellular vesicles （LEVs） in the plasma of DVT patients and investigated whether microRNAs （miRNAs） enriched in these LEVs could serve as new biomarkers. While the total number of LEVs in patients with DVT was comparable to the control group, there was an increase in platelet-derived LEVs. Specifically, 13 miRNAs were decreased while 4 miRNAs were increased in LEVs in DVT patients （DVT LEVs）, among which miR-4485-5p showed a significant 10.9-fold increase, demonstrating a good diagnostic performance for DVT with an area under the curve of 0.81.<br>  Overexpression of miR-4485-5p in human umbilical vein endothelial cells（ HUVEC） led to the suppression of tissue plasminogen activator, a predicted target of miR-4485p and a key component of the fibrinolytic system. Additionally, co-culture of HUVEC with DVT LEVs resulted in increased intracellular miR-4485-5p. These findings suggest that miR-4485-5p in platelet-derived LEVs could serve as a valuable biomarker for DVT and may contribute to thrombus formation by suppressing the fibrinolytic system.