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

摘要

Objective: Soluble vascular endothelial growth factor receptor1 (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 receptor1 gene and caused up-regulation of heme oxygenase1, a cytoprotective enzyme found to be dysfunctional in preeclampsia. Conclusion: In summary, resveratrol can inhibit sFlt-1 release and up-regulate heme oxygenase1; thus, may offer therapeutic potential in preeclampsia.