title: Hypoxic trophoblast-derived sFlt-1 may contribute to endothelial dysfunction: implication for the mechanism of trophoblast-endothelial dysfunction in preeclampsia.
abstract: The maternal systemic disorder of widespread endothelial dysfunction is a primary focus in understanding the development of preeclampsia. sFlt-1 (soluble fms-like tyrosine kinase receptor 1), an endogenous inhibitor of VEGF (vascular endothelial growth factor), may play important roles in endothelial dysfunction. The present study aimed to determine whether hypoxic trophoblast-derived sFlt-1 could lead to endothelial dysfunction by establishing a cocultured model of anoxic TEV-1s (human first-trimester extravillous trophoblasts) and HUVECs (human umbilical vein endothelial cells). The results showed that the hypoxic treatment significantly promoted sFlt-1 mRNA and protein expression in TEV-1s in a time-dependent manner compared with the effect in HUVECs. When HUVECs were cocultured with anoxic TEV-1s, the endothelial function, which was characterized by NO (nitric oxide) synthesis and monolayer barrier function of HUVECs, were notably decreased, accompanied by increasing sFlt-1 and decreasing VEGF in cell-conditioned medium. Moreover, the observed endothelial dysfunction described above was consistent with the dysfunction observed in VEGF siRNA-treated cultures. The findings presented herein imply that chronically hypoxic trophoblasts may release sufficient sFlt-1 to cause endothelial dysfunction by depriving cells of VEGF activity.
authors.affiliation: Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Peoples Republic of China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Zhou
authors.forename: Fu-Yuan
authors.initials: FY
authors.lastname: Qiao
authors.forename: Chang
authors.initials: C
authors.lastname: Zhao
authors.forename: Hai-Yi
authors.initials: HY
authors.lastname: Liu
mesh_terms: D002450:Cell Communication; D015687:Cell Hypoxia; D002478:Cells, Cultured; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology; D005260:Female; D006801:Humans; D009569:Nitric Oxide / Q000096:biosynthesis; D011225:Pre-Eclampsia / Q000378:metabolism; D011247:Pregnancy; D034741:RNA, Small Interfering / Q000235:genetics; D014327:Trophoblasts / Q000502:physiology*; D014471:Umbilical Veins / Q000166:cytology; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000096:biosynthesis / Q000502:physiology*
chemical_list: D034741:RNA, Small Interfering; D042461:Vascular Endothelial Growth Factor A; D009569:Nitric Oxide; D040281:Vascular Endothelial Growth Factor Receptor-1