miR-150 regulates endothelial progenitor cell differentiation via Akt and promotes thrombus resolution.

Background: Deep venous thrombosis (DVT) constitutes a major global disease burden. Endothelial progenitor cells (EPCs) have been described in association with recanalization of venous thrombus. Furthermore, emerging evidence suggests microRNAs are involved in this progression. The goal of this study was to investigate the influence of miR-150 on the behavior of EPCs and its potential contribution in venous thrombosis resolution.

Methods: We isolated and cultured EPCs from healthy adults. Next, early EPCs or endothelial colony-forming cells (ECFCs or late EPCs) were transfected with miR-150 agomir and antagomir. Gene expression profiles, proliferation, cytokine secretion, and angiogenic capacity of early EPCs and ECFCs were examined. The effects of miR-150 on c-Myb expression and Akt/FOXO1 signaling were also evaluated. Furthermore, a rat model of venous thrombosis was constructed to determine the in vivo function of EPCs.

Results: Our results showed that miR-150 overexpression in early EPCs significantly promoted differentiation to ECFCs and contributed to proliferation and tube formation. However, suppression of miR-150 in late EPCs inhibited proliferation and tube formation. Moreover, we identified that this progression is regulated by inhibition of c-Myb and activation of the Akt/FOXO1 pathway. Our findings also showed that miR-150 led to the enhanced resolution ability of EPCs in a rat venous thrombosis model.

Conclusions: In this study, we present a novel mechanism of miRNA-mediated regulation of EPCs and Akt activation in thrombus resolution.