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

Abstract

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 DVTmice. 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

TXNIP activates NLRP3/IL-1β and participate in inflammatory response and oxidative stress to promote deep venous thrombosis

“…14 Feng et al reported that TXNIP expression was elevated in DVT mice. 15 Our result was similar to their research. However, there is still no clear evidence about TXNIP interact with NLRP3 in DVT formation.…”

“…13 An increasing number of studies have indicated that TXNIP participated in the formation of thrombosis. 14,15 However, there is no clear evidence presents the change of TXNIP in DVT. In our study, we first investigated the changes of TXNIP and NLRP3 levels at different times after DVT.…”

Non-coding RNAs regulating endothelial progenitor cells for venous thrombosis: promising therapy and innovation

“…Additionally, the angiogenesis and migration of EPCs are enhanced by miR-126 exosomes [ 94 ], thereby regulating the recanalization of DVT. A recent study has shown that miR-136-5p from EPC-released extracellular vesicles facilitates the dissolution of DVT by inhibiting TXNIP expression, providing a promising treatment target for DVT [ 95 ].…”

MiRNAs and Their Role in Venous Thromboembolic Complications

“…The authors concluded that the aberrant expression of circulating miR-424-5p and miR-136-5p was associated with hypercoagulability. At the same time, one of the studies demonstrated the action of endothelial progenitor cell-released extracellular vesicles (EPC-EVs) for transferring miR-136-5p in DVT [81]. It was shown that initially, miR-136-5p expression was suppressed and that the thioredoxin-interacting protein (TXNIP) expression was elevated in DVT mice.…”