P 42 Down-regulation of The Nr2-regulated gene heme oxygenase-1 (HO-1) in the placenta from patients with early-onset preeclampsia

Abstract

Introduction and objective Increased oxidative stress and diminished oxidative capacity are distinctive features in the pregnancy-specific syndrome preeclampsia (PE). Activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) initiates and enhances the transcription of many antioxidative enzymes such as heme oxygenase-1 (HO-1), which participates in the exposure to reactive oxygen species and protects the trophoblast-like cells against oxidative injury. HO-1 is an important mediator of the pro-angiogenic activity of the vascular endothelial growth factor VEGF. In this study we analysed the placental protein expression of Nrf2 and HO-1 in the placentas from normal pregnancies and those complicated with early-onset preeclampsia. Patients and methods 12 placentas from patients complicated with early-onset preeclampsia were analysed and compared to normal placentae from 11 healthy normotensive women (29–33 weeks gestation). The protein extracts were subjected to western blotting using anti-Nrf2 and anti-HO-1 antibodies. The serum levels of VEGF and sFlt-1 were estimated using ELISA. Results As expected the sFlt-1/VEGF ratio was increased in patients with early-onset preeclampsia R > 440 compared to normotensive ones (p Conclusion These data reveal a novel mechanism by which the decreased expression of HO-1 during PE may be involved in the pathogenesis of this syndrome. Interestingly, this does not correlate with the expression of Nrf2 in preeclamptic placentas. Nrf2 is the major transcriptional regulator of HO-1 and possible alterations in post-translational Nrf2 regulation of antioxidative enzymes in early-onset PE will be a subject of our further research.