ABSTRACT
Placentation,which is critical for maternal-fetal exchange of nutrients and gases,is a complicated process comprising stepwise vasculogenesis and angiogenesis.Hypoxia caused by impairedtrophoblast invasion may cause various angiogenic abnormalities in human placenta.The Notchl signaling pathway plays an important role in the regulation of angiogenesis.The angiogenesis of human umbilical vein endothelial cells (HUVECs) under normal/hypoxic conditions and the mRNA/protein level of Notchl/Dell4/Jaggedl were investigated in this study.The effects of DAPT/JAG-1 on the migration of HUVECs were also assessed by cell wound healing assay,so as to discover the possible role of notchl signaling pathway in the angiogenesis of human placenta.The results showed that angiogenic ability of HUVECs was seriously reduced under hypoxic conditions.The mRNA and protein levels of Notchl/Dell4/Jaggedl were decreased in the hypoxic group compared to the control one.In addition,the migration capability of HUVECs was significantly obstructed when treated with DAPT and under hopoxic condition,but promoted when treated with JAG-1.The above results demonstrate that hypoxia downregulates the angiogenesis in human placenta via Notch 1 signaling pathway.
ABSTRACT
The mechanism of injury on the human glomerular endothelial cells (ciGENC) induced by preeclampsia serum was investigated.Concentration of maternal serum sFlt-1 protein was detected by ELISA.Fluorescently-labeled bovine serum albumin infiltrating through lower chamber of Transwell was measured by multifunction microplate reader.Morphologic change of ciGENC was observed under inverted phase contrast microscope.The concentration of sflt-1 in preeclampsia groups was significantly increased as compared with control group (P＜0.01).Permeability in preeclampsia groups was significantly increased as compared with control group (P＜0.01).By contrast with severe preeclampsia group,the permeability of ciGENC monolayer in mild preeclampsia group was decreased significantly (P＜0.05).Intervention of exogenous VEGF significantly decreased permeability of ciGENC in preeclampsia groups.It was concluded that sFlt-1 increased ciGENC permeability by damaging integrity of endothelial barrier function.
ABSTRACT
This study examined the effect of over-expression of sFlt-1 by trophoblasts on the barrier function of glomerular endothelial cells and the role of VEGF in this process in order to explore the pathogenesis of glomerular disease in preeclampsia.SFlt-1 expression in the human trophoblasts (TEV-1 cells) was enhanced by transfecting sFlt-1 plasmid DNA into TEV-1 cells.The monolayer barrier function of glomerular endothelial cells (ciGEnCs) was determined by measuring the fluorescence intensity of bovine serum albumin (BSA) that crossed the monolayer of glomerular endothelial cells.The results showed that the over-expression of sFlt-1 by TEV-1 cells led to the barrier dysfunction of ciGEnCs,and the exogenous VEGF could alleviate the ciGEnCs dysfunction resulting from the over-expression of sFlt-1 to a certain extent.It was concluded that the dysregulation of sFlt-1 and VEGF in preeclamptic pregnancy may contribute to the barrier dysfunction of glomerular endothelial cells,and VEGF may play an important role in maintaining the barrier function of glomerular endothelial cells,but it may not be the sole factor.