microRNA‑646 inhibits angiogenesis of endothelial progenitor cells in pre‑eclamptic pregnancy by targeting the VEGF‑A/HIF‑1α axis

Abstract

Pre-eclampsia is a complication that occurs during pregnancy, the pathological feature of which is a change in vascular endothelial homeostasis. microRNA (miR)-646 is an anti-angiogenic miRNA that has been indicated to exhibit potential anti-angiogenic effects in endothelial cells cultured in vitro and in ischemia-induced angiogenesis. However, whether miR-646 has therapeutic potential in placental angiogenesis in pre-eclampsia remains to be determined. In the current study, human peripheral blood-derived endothelial progenitor cells (EPCs) were isolated to study the coordination between miR-646, vascular endothelial growth factor (VEGF)-A and hypoxia-inducible factor (HIF)-1 alpha expression in preeclampsia EPCs. EPCs were isolated from human peripheral blood to demonstrate a potential interaction between miR-646 and targets (VEGF-A) in vitro. The number of EPCs and the expression of miR-646 in patients with preeclampsia was detected, and the effects of miR-646 on EPC function and preeclampsia angiogenesis was assessed. Clinical specimens demonstrated that miR-646 expression was enhanced in pregnancy with preeclampsia. The results indicated that miR-646 suppressed EPCs multiplication, differentiation and migration. miR-646 was observed to exert an anti-angiogenic function by suppressing the expression of angiogenic cytokines VEGF-A and HIF-1 alpha. Additionally, luciferase results displayed that miR-646 downregulated VEGF-A expression by directly binding to a specific sequence in its 3'-untranslated region. The results of the current study demonstrated that the miR-646/VEGF-A/HIF-1 alpha axis is significant for angiogenic properties of EPCs in vitro and in vivo placental vasculogenesis. The results of the present study provide a new insight into microRNA regulation of vessel homeostasis and angiogenesis, and a basis for alternative treatments for patients with pre-eclampsia.