Notch1 Impairs Endothelial Progenitor Cell Bioactivity in Preeclampsia

Aberrant vasculature and endothelial dysfunction on both the maternal and the fetal side are thought to play a role in the pathogenesis of preeclampsia, a hypertensive complication during pregnancy. Endothelial progenitor cells (EPCs) have the capacity for endothelial repair. The Dll4/Notch signaling pathway suppresses the functions of EPCs in the pathogenesis of preeclampsia. Notch1 was found to be one of the specific receptors for ligands of the Delta 4 and play critical roles in angiogenesis. However, the roles of Notch1 with regard to EPCs and preeclampsia have yet to be completely characterized. The aim of this study is to determine whether Notch1 also has a negative influence on the regulation of EPC activity. Accordingly, we analyzed the differences between the preeclampsia group and the control group in terms of the number of EPCs and colony-forming units (CFUs) and their Notch1 expressions. The influence of the Notch1 signaling pathway on functions of EPCs was determined by repeating the assays in the presence of Notch1 downregulation. The number of EPCs and CFUs was significantly lower in patients with preeclampsia compared to healthy controls. Additionally, there was a notable increase in Notch1 expression in EPCs of patients with preeclampsia compared to controls. The downregulation of Notch1 promoted the proliferation, differentiation, migration, and adhesion of EPCs and the ability to form human umbilical vein endothelial cell tubes. These findings suggested that decrease and dysfunction of EPCs may be involved in the pathogenesis of preeclampsia. Inhibition of Notch1, which promoted EPC-mediated angiogenesis in vitro, may be an alternative therapeutic approach to promoting vasculogenesis in patients with preeclampsia.