Abstract

BACKGROUND: Endothelial progenitor cells (EPCs) play an important role in therapeutic angiogenesis. Besides, resveratrol (RSV) exerts many pharmacological functions in regulation of cell function. Furthermore, microRNAs (miRNAs) have been considered to be of great significance in biological process. In this study, we aimed to investigate the effect of RSV on EPCs and its potential mechanism that involved in recanalization of venous thrombosis.

MATERIAL AND METHODS: EPCs were treated with RSV, and angiogenic functions was evaluated by tube formation and migration assays. miR-542-3p expression level in EPCs was assessed and exogenously modified. Bioinformatic analysis was applied to detect the potential target of miR-542-3p. Effects of RSV treatment in vivo venous thrombosis rat model were evaluated.

RESULTS: RSV enhanced angiogenic function of EPCs and decreased expression of miR-542-3p. Dual luciferase reporter gene and western blot results confirmed angiopoietin-2 (ANGPT2) was a direct target of miR-542-3p. It was found that inhibition of miR-542-3p contributed to angiogenesis of EPCs and elevated ANGPT2 protein level. Finally, in a rat model of venous thrombosis, RSV-treated EPCs promoted recanalization of thrombi.

CONCLUSIONS: We demonstrated that RSV can contribute to progenitor cells angiogenesis via miR-542-3p by targeting ANGPT2, subsequently enhanced recanalization of thrombi.

Keywords: MicroRNAs, Neovascularization, Pathologic, Stem Cells, Venous Thrombosis, Adult, Angiopoietin-2, Base Sequence, Cell Movement, Cell Survival, endothelial progenitor cells, Neovascularization, Physiologic, Rats, Nude, resveratrol