Xiaoxia Liu1, Qingqing Luo1, Yanfang Zheng1, Xiaoping Liu1, Ying Hu1, Fang Wang1, Li Zou2. 1. Department of Obstetrics and Gynecology, Union Hospital, Huazhong University of Science and Technology, Wuhan 430022, China. 2. Department of Obstetrics and Gynecology, Union Hospital, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: medzouli@163.com.
Abstract
INTRODUCTION: Preeclampsia is a hypertensive complication in pregnancy, closely related to endothelial dysfunction. Endothelial progenitor cells (EPCs) have the capacity for endothelial repair. Both Ephrin-B2 and Dll4/Notch pathway play critical roles in various steps of angiogenesis. In addition, there is an up-regulation of ephrin-B2 expression consequent to Dll4/Notch activation in endothelial cells (ECs). However, the roles of ephrin-B2 and Dll4/Notch signaling on EPCs, as well as the relationship between them, have not been completely characterized. METHODS: We analyzed expression of ephrin-B2 in the EPCs and placenta from preeclampsia and normal pregnancy. Then up-regulation and down-regulation strategies were employed to detect the effects of ephrin-B2 on EPC proliferation, differentiation, migration and HUVEC-tube formation. The effects of Dll4/Notch signaling on EPCs' functions were determined by repeating the assays in the presence of Dll4 or DAPT as agonists or antagonists of Notch signaling, respectively. RESULTS: Ephrin-B2 expression increased notably in preeclampsia EPCs and placenta, compared with controls. Up-regulation of ephrin-B2 impaired EPCs' proliferation, differentiation, migration and HUVEC-tube formation capabilities. In contrast, down-regulation of ephrin-B2 in EPCs, resulted in the opposite effects. In addition, activation of Dll4/Notch signaling led to increased expression of ephrin-B2 and subsequent inhibition of EPCs activity. DISCUSSION: Ephrin-B2, a downstream of Dll4/Notch signaling pathway, might be act as an inhibitor of EPC-mediated vasculogenesis in vitro, as well as a potential target in the effort to promote angiogenesis of patients with preeclampsia.
INTRODUCTION: Preeclampsia is a hypertensive complication in pregnancy, closely related to endothelial dysfunction. Endothelial progenitor cells (EPCs) have the capacity for endothelial repair. Both Ephrin-B2 and Dll4/Notch pathway play critical roles in various steps of angiogenesis. In addition, there is an up-regulation of ephrin-B2 expression consequent to Dll4/Notch activation in endothelial cells (ECs). However, the roles of ephrin-B2 and Dll4/Notch signaling on EPCs, as well as the relationship between them, have not been completely characterized. METHODS: We analyzed expression of ephrin-B2 in the EPCs and placenta from preeclampsia and normal pregnancy. Then up-regulation and down-regulation strategies were employed to detect the effects of ephrin-B2 on EPC proliferation, differentiation, migration and HUVEC-tube formation. The effects of Dll4/Notch signaling on EPCs' functions were determined by repeating the assays in the presence of Dll4 or DAPT as agonists or antagonists of Notch signaling, respectively. RESULTS:Ephrin-B2 expression increased notably in preeclampsia EPCs and placenta, compared with controls. Up-regulation of ephrin-B2 impaired EPCs' proliferation, differentiation, migration and HUVEC-tube formation capabilities. In contrast, down-regulation of ephrin-B2 in EPCs, resulted in the opposite effects. In addition, activation of Dll4/Notch signaling led to increased expression of ephrin-B2 and subsequent inhibition of EPCs activity. DISCUSSION: Ephrin-B2, a downstream of Dll4/Notch signaling pathway, might be act as an inhibitor of EPC-mediated vasculogenesis in vitro, as well as a potential target in the effort to promote angiogenesis of patients with preeclampsia.