Curcumin promotes venous thrombi resolve process in a mouse deep venous thrombosis model via regulating miR-499

The morbidity of deep venous thrombosis (DVT) is increasing rapidly and the current therapeutic strategies for DVT are unsatisfactory. Accumulating evidence suggest that venous thrombi resolve (VTR) may provide new insights into DVT therapeutic strategies. The aim of this study was to investigate the role of curcumin in VTR process and try to reveal the potential mechanism.

Immunofluorescence and HE staining were performed to investigate the therapeutic angiogenesis effect of curcumin in VTR process. Microarray analysis and RT-PCR were performed to examine the expression level of miR-499 in thrombosis after curcumin administration. Cell proliferation, migration and angiogenesis capacity were tested by CCK8 assay, Transwell assay and Tube formation assay, respectively. Dual-luciferase reporter assay (DLR) was used to confirm the connection between miR-499 and paired phosphate and tension homology deleted on chromosome ten (PTEN).

We found that curcumin could effectively promote VTR process by activating angiogenesis in thrombus in vivo. The expression of miR-499 exhibited notably downregulated after curcumin administration. The proangiogenic effect of curcumin in HUVECs could be blocked by miR-499 overexpression. In addition, we confirmed that miR-499 directly target to the 3'UTR region of PTEN.

Curcumin promotes VTR process in DVT through activating therapeutic angiogenesis. Mechanically, curcumin promotes therapeutic angiogenesis by regulating miR-499 mediated PTEN/VEGF/Ang-1 signaling pathway.