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Hypoxic trophoblast-derived sFlt-1 may contribute to endothelial dysfunction: implication for the mechanism of trophoblast–endothelial dysfunction in preeclampsia
Qiong Zhou*, Fu‑Yuan Qiao*, Chang Zhao† and Hai‑Yi Liu*1
*Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Peoples Republic of China, and †Department of Surgery, Wuhan No.8 Hospital, Wuhan 430030, Peoples Republic of China
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.
Key words: endothelium dysfunction, preeclampsia, sFlt-1, trophoblast cell, VEGF
Abbreviations: FBS, fetal bovine serum, HUVECs, human umbilical vein endothelial cells, NO, nitric oxide, sFlt-1, soluble fms-like tyrosine kinase receptor 1, siRNA, small interfering RNA, TEV-1, human first-trimester extravillous trophoblasts, VEGF, vascular endothelial growth factor
1To whom correspondence should be addressed (email firstname.lastname@example.org).
Received 10 January 2010/29 June 2010; accepted 9 September 2010
Published as Cell Biology International Immediate Publication 9 September 2010, doi:10.1042/CBI20100020
© The Author(s) Journal compilation © 2011 Portland Press Limited