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Pregnancy Hypertens. 2013 Apr;3(2):74. doi: 10.1016/j.preghy.2013.04.048. Epub 2013 Jun 06.

PP020. Evidence of a preventive role of Nrf2 in preeclampsia.

Pregnancy hypertension

Nisreen Kweider, Christoph Jan Wruck, Andreas Ludwig, Daniela Dreymueller, Tamme Goecke, Ulrich Pecks, Thomas Pufe, Werner Rath

PMID: 26105875 DOI: 10.1016/j.preghy.2013.04.048

Abstract

INTRODUCTION: Smoking during pregnancy is associated with lower preeclampsia risk. This has been mainly explained through the effect of carbon monoxide CO.

OBJECTIVES: Recent studies showed that the activation of heme oxygenase-1 HO-1 and consequently its metabolite CO in cultured cells mediated an inhibition of sFlt-1 and sEng release, and an up-regulation of the endogenous VEGF. The transcriptional regulation of the HO-1 gene is majorly regulated through the transcription factor Nrf2. The aim of this study was to investigate in vitro the effect of HO-1-activation via Nrf2 on the pro- and anti-angiogenic factors.

METHODS: BeWo cells and HUVECs endothelial cells were used to study the angiogenic effect of Nrf2-activation. ELISA, scratch and tube formation assay were mainly applied.

RESULTS: The activation of HO-1 via Nrf2 lead to an increase in the protein levels of VEGF (control 64.75pg/ml±4.3; Sulforaphane-treated cells 128.2pg/ml±6.5 p<0.005) and decrease in the augmented sFlt-1 in the supernatant of the treated cells (control 186.3pg/ml±28.7; H2O2-treatment 2026pg/ml±64, co-treatment with H2O2 and Sulforaphane 1200pg/ml±19.7 p<0.01). Up-regulation of HO-1/CO enhanced tube formation and migration of the endothelial cells.

CONCLUSION: The activation of HO-1/CO via Nrf2 inducer such as sulforaphane inhibited in vitro the release of sFlt-1, thus the activation of Nrf2 during the first trimester may improve the balance of the pro- and anti-angiogenic factors.

Copyright © 2013. Published by Elsevier B.V.

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