Antiangiogenic effect of soluble vascular endothelial growth factor receptor-1 in placental angiogenesis

Research output: Contribution to journalArticle

Abstract

Differential splicing of the flt-1 mRNA generates soluble variant of vascular endothelial growth factor (VEGF) receptor-1 (sVEGFR-1, also known as sFlt-1). The action of VEGF is antagonized by sVEGFR-1. Soluble VEGFR-1 binds to VEGF with a high affinity and therefore works to modulate VEGF and VEGF signaling pathway. In this study, the authors tested the hypothesis that VEGF-mediated endothelial cell angiogenesis is tightly modulated by the release of sVEGFR-1 and placental expression of sVEGFR-1 is upregulated by hypoxia. Immunolocalization studies showed progressively intense staining for sVEGFR-1 and VEGF in the trophoblast of placental villous explants throughout gestation. Endothelial cell migration studies using a modified Boyden's chamber showed a significant increase in cell migration in response to VEGF that was significantly attenuated in the presence of exogenous sVEGFR-1. Furthermore, stimulation of endothelial cells with VEGF led to a dose-dependent increase in the release of sVEGFR-1 as determined by enzyme-linked immunosorbent assay (ELISA). Exposure of normal placental villous explants to hypoxia (1% pO2) increased trophoblast expression of sVEGFR-1 when compared with tissue normoxia (5% pO2). In addition, conditioned media from hypoxia treated placental villous explants induced a significant increase in endothelial cell migration that was significantly reduced in presence of sVEGFR-1. Our study demonstrates that hypoxia positively regulates sVEGFR-1 protein expression in ex vivo trophoblasts, which control VEGF-driven angiogenesis.

Original languageEnglish
Pages (from-to)89-95
Number of pages7
JournalEndothelium
Volume12
Issue number1-2
DOIs
Publication statusPublished - 2005

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Vascular Endothelial Growth Factor Receptor-1
Vascular Endothelial Growth Factor A
Trophoblasts
Endothelial Cells
Cell Movement
Conditioned Culture Medium
Enzyme-Linked Immunosorbent Assay
Staining and Labeling
Pregnancy
Messenger RNA

Keywords

  • angiogenesis
  • hypoxia
  • preeclampsia
  • vascular endothelial growth factor receptor

Cite this

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title = "Antiangiogenic effect of soluble vascular endothelial growth factor receptor-1 in placental angiogenesis",
abstract = "Differential splicing of the flt-1 mRNA generates soluble variant of vascular endothelial growth factor (VEGF) receptor-1 (sVEGFR-1, also known as sFlt-1). The action of VEGF is antagonized by sVEGFR-1. Soluble VEGFR-1 binds to VEGF with a high affinity and therefore works to modulate VEGF and VEGF signaling pathway. In this study, the authors tested the hypothesis that VEGF-mediated endothelial cell angiogenesis is tightly modulated by the release of sVEGFR-1 and placental expression of sVEGFR-1 is upregulated by hypoxia. Immunolocalization studies showed progressively intense staining for sVEGFR-1 and VEGF in the trophoblast of placental villous explants throughout gestation. Endothelial cell migration studies using a modified Boyden's chamber showed a significant increase in cell migration in response to VEGF that was significantly attenuated in the presence of exogenous sVEGFR-1. Furthermore, stimulation of endothelial cells with VEGF led to a dose-dependent increase in the release of sVEGFR-1 as determined by enzyme-linked immunosorbent assay (ELISA). Exposure of normal placental villous explants to hypoxia (1{\%} pO2) increased trophoblast expression of sVEGFR-1 when compared with tissue normoxia (5{\%} pO2). In addition, conditioned media from hypoxia treated placental villous explants induced a significant increase in endothelial cell migration that was significantly reduced in presence of sVEGFR-1. Our study demonstrates that hypoxia positively regulates sVEGFR-1 protein expression in ex vivo trophoblasts, which control VEGF-driven angiogenesis.",
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Antiangiogenic effect of soluble vascular endothelial growth factor receptor-1 in placental angiogenesis. / Ahmad, Shakil; Ahmed, Asif.

In: Endothelium, Vol. 12, No. 1-2, 2005, p. 89-95.

Research output: Contribution to journalArticle

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AU - Ahmed, Asif

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