PP019. A new player in preeclampsia: The NF-E2-related factor 2 (NRF2)

Preeclampsia PE is characterized by diminished antioxidant capacity. These enzymes are mainly regulated via the transcription factor Nrf2.

PE is associated with an increase in Nrf2 activity. Nrf2 involves also in the vascular homeostasis during PE. Respective hemodisturbances have been associated with impaired invasion of the extravillous trophoblast EVT in early onset IUGR associated with PE. To test this link, we studied in vitro the interaction between Nrf2 and VEGF, then their expression was determined in third trimester placental beds in cases of severe early onset IUGR/PE.

BeWo cells were used in the in vitro study.Western blot; ELISA and Dual Luciferase assay were applied. Full-thickness uterine tissues from 6 healthy and 6 women with severe early onset IUGR/PE were used to study the expression of VEGF, Nrf2 and 4-HNE in the EVT.

Nrf2-activation and its downstream target protein HO-1 augmented CO production, which in turn up-regulated the expression of VEGF. EVT in cases with IUGR/PE showed increased expression of Nrf2 and decreased VEGF intensity.

In early onset IUGR/PE the EVT experience oxidative stress and try to counteract this by increased expression of Nrf2. However, since these cells fail to up-regulate VEGF, Nrf2-activation does not occur, leading to further trophoblast damage. At the same time, in vitro data show a protective role of the Nrf2/HO-1 pathway, which may have a therapeutic potential in PE.