MicroRNA-136-5p from Endothelial Progenitor Cells-released Extracellular Vesicles Mediates TXNIP to Promote the Dissolution of Deep Venous Thrombosis.

Objective: Endothelial progenitor cells-released extracellular vesicles (EPCs-EVs) have previously been reported to promote the dissolution of deep venous thrombosis (DVT) through delivery of microRNA (miR). Given that, this research was projected to search the relative action of EPCs-EVs transferring of miR-136-5p in DVT.

Methods: From EPCs transfected with miR-136-5p agomir or antagomir, EVs were extracted and then injected into DVT mice. Meanwhile, based on the treatment with EPCs-EVs loading miR-136-5p antagomir, silenced thioredoxin-interacting protein (TXNIP) lentivirus was injected into DVT mice to perform the rescue experiments. Afterwards, the length and weight of venous thrombosis, EPC apoptosis and inflammatory factors, plasmin, fibrinogen, and thrombin-antithrombin were measured. miR-136-5p and TXNIP expression in DVT mice, and their targeting relationship were evaluated.

Results: miR-136-5p expression was suppressed and TXNIP expression was elevated in DVT mice. EPCs-EV reduced the length and weight of venous thrombosis, suppressed cell apoptosis and inflammatory reaction, as well as elevated level of plasmin, and reduced levels of fibrinogen and thrombin-antithrombin in DVT mice. Restored miR-136-5p loaded by EPCs-EV further attenuated DVT but EPCs-EV transfer of depleted miR-136-5p resulted in the opposite consequences. miR-136-5p targeted TXNIP and silenced TXNIP rescued the effect of EPCs-EV transfer of depleted miR-136-5p on DVT.

Conclusion: miR-136-5p from EPCs-EV suppresses TXNIP expression to reduce the thrombus size in DVT, offering a promising treatment target for DVT.