Gould, Phillip S., Gu, Mei, Liao, Jianqin, Ahmad, Shakil, Cudmore, Melissa J., Ahmed, Asif and Vatish, Manu. (2010) Upregulation of Urotensin II receptor in preeclampsia causes in vitro placental release of soluble vascular endothelial growth factor receptor 1 in hypoxia. Hypertension, Vol.56 (No.1). pp. 172-178. ISSN 0194-911X

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Abstract

Preeclampsia is a hypertensive disorder of pregnancy caused by abnormal placental function, partly because of chronic hypoxia at the utero-placental junction. The increase in levels of soluble vascular endothelial growth factor receptor 1, an antiangiogenic agent known to inhibit placental vascularization, is an important cellular factor implicated in the onset of preeclampsia. We investigated the ligand urotensin II (U-II), a potent endogenous vasoconstrictor and proangiogenic agent, for which levels have been reported to increase in patients with preeclampsia. We hypothesized that an increased sensitivity to U-II in preeclampsia might be achieved by upregulation of placental U-II receptors. We further investigated the role of U-II receptor stimulation on soluble vascular endothelial growth factor receptor 1 release in placental explants from diseased and normal patients. Immunohistochemistry, real-time PCR, and Western blotting analysis revealed that U-II receptor expression was significantly upregulated in preeclampsia placentas compared with controls (P < 0.01). Cellular models of syncytiotrophoblast and vascular endothelial cells subjected to hypoxic conditions revealed an increase in U-II receptor levels in the syncytiotrophoblast model. This induction is regulated by the transcriptional activator hypoxia-inducible factor 1 alpha. U-II treatment is associated with increased secretion of soluble vascular endothelial growth factor receptor 1 only in preeclamptic placental explants under hypoxia but not in control conditions. Interestingly, normal placental explants did not respond to U-II stimulation. (Hypertension. 2010; 56: 172-178.)

Item Type:	Journal Article
Subjects:	R Medicine > RC Internal medicine
Divisions:	Faculty of Medicine > Warwick Medical School > Clinical Sciences Research Institute (CSRI) Faculty of Medicine > Warwick Medical School > Reproductive Health Faculty of Medicine > Warwick Medical School
Journal or Publication Title:	Hypertension
Publisher:	American Heart Association
ISSN:	0194-911X
Date:	1 July 2010
Volume:	Vol.56
Number:	No.1
Number of Pages:	7
Page Range:	pp. 172-178
Identification Number:	10.1161/HYPERTENSIONAHA.110.152074
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Restricted or Subscription Access
Funder:	Wellcome Trust, Warwick Private Hospitals Charitable Trust, Fulbright Commission, Medical Research Council, European Vascular Genomics Network
Grant number:	G0601295, G0700288, LSHM-CT-2003-503254
URI:	http://wrap.warwick.ac.uk/id/eprint/5689

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