Resveratrol inhibits the release of soluble fms-like tyrosine kinase (sFlt-1) from human placenta

Melissa J. Cudmore, Wenda Ramma, Meng Cai, Takeshi Fujisawa, Shakil Ahmad, Bahjat Al-Ani, Asif Ahmed

Research output: Contribution to journalArticlepeer-review

Abstract

Objective - Soluble vascular endothelial growth factor receptor–1 (also know as soluble fms-like tyrosine kinase [sFlt]-1) is a key causative factor of preeclampsia. Resveratrol, a plant phytoalexin, has antiinflammatory and cardioprotective properties. We sought to determine the effect of resveratrol on sFlt-1 release.

Study Design - Human umbilical vein endothelial cells, transformed human trophoblast-8 (HTR/SVneo)-8/SVneo trophoblast cells, or placental explants were incubated with cytokines and/or resveratrol. Conditioned media were assayed for sFlt-1 by enzyme-linked immunosorbent assay and cell proteins used for Western blotting.

Results - Resveratrol inhibited cytokine-induced release of sFlt-1 from normal placental explants and from preeclamptic placental explants. Preincubation of human umbilical vein endothelial cells or HTR-8/SVneo cells with resveratrol abrogated sFlt-1 release. Resveratrol prevented the up-regulation of early growth response protein-1 (Egr-1), a transcription factor necessary for induction of the vascular endothelial growth factor receptor–1 gene and caused up-regulation of heme oxygenase–1, a cytoprotective enzyme found to be dysfunctional in preeclampsia.

Conclusion - In summary, resveratrol can inhibit sFlt-1 release and up-regulate heme oxygenase–1; thus, may offer therapeutic potential in preeclampsia.
Original languageEnglish
Pages (from-to)253.e10–253.e15
Number of pages6
JournalAmerican Journal of Obstetrics and Gynecology
Volume206
Issue number3
DOIs
Publication statusPublished - Mar 2012

Keywords

  • endothelial cells
  • heme oxygenase–1
  • placenta
  • resveratrol
  • soluble fms-like tyrosine kinase–1

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