PP020. Evidence of a preventive role of Nrf2 in preeclampsia

Abstract

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