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

Cudmore, Melissa J., Ramma, Wenda, Cai, Meng, Fujisawa, Takeshi, Ahmad, Shakil, Al-Ani, Bahjat and Ahmed, Asif (2012). Resveratrol inhibits the release of soluble fms-like tyrosine kinase (sFlt-1) from human placenta. American Journal of Obstetrics and Gynecology, 206 (3), 253.e10–253.e15.


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.

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Divisions: Life & Health Sciences > Biosciences
Aston Medical School
Life & Health Sciences
Uncontrolled Keywords: endothelial cells,heme oxygenase–1,placenta,resveratrol,soluble fms-like tyrosine kinase–1,Obstetrics and Gynaecology
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Published Date: 2012-03
Authors: Cudmore, Melissa J.
Ramma, Wenda
Cai, Meng ( 0000-0002-0864-667X)
Fujisawa, Takeshi
Ahmad, Shakil ( 0000-0002-9294-0475)
Al-Ani, Bahjat
Ahmed, Asif


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