O18. Oxidative stress in preeclampsia

Preeclampsia (PE) is characterized by hypertension and proteinuria that affects 5–10% of pregnancies. Risk factors of PE cause the release of reactive oxygen species, which lead to increased vascular cell proliferation and hypertrophy, apoptosis, inflammation and extracellular matrix remodeling. Our purpose was the complex monitoring of in vivo oxidative stress in preeclamptic patients in order to find possible biomarkers that might be used in the prognosis or in the early diagnosis of PE. We examined the effects of oxidative stress on the level of proteins by measuring thiol content on the surface of peripheral blood mononuclear cells (PBMC) and circulating extracellular vesicles by DyLightMaleimide staining and also in the plasma by DTNB assay. The oxidative damage of DNA was measured by flow cytometric detection of oxoguanin-8. Multicolor FACS was used for the investigation of the regulatory molecules of the redox homeostasis including the expression levels of sirtuin 3, 4, 5, and both the cell surface and intracellular expression of thioredoxin1 (TRX1) and peroxiredoxin1 (PRDX1) in PBMC. Plasma soluble PRDX1 level was also detected by ELISA. The total exofacial thiol content of PBMC was significantly higher in preeclamptic women, implying increased activation of these immune cells, and the total thiol content of plasma proteins was also elevated. In contrast, we could not detect any differences in the oxoguanine 8 expression of PBMCs, a marker of oxidative DNA damage. Significantly higher expression levels of extracellular PRDX1 and lower content of intracellular PRDX1 were detected in preeclamptic patients. The intracellular PRDX1 content of lymphocytes and monocytes showed positive correlations with the plasma soluble PRDX1 level in PE. Both the cell surface expression and the intracellular content of TRX1 were significantly higher both in lymphocytes and monocytes in the preeclamptic group. The levels of intracellular Trx1 and Prdx1 are known to increase under inflammatory conditions. They act as direct ROS scavengers, as molecular chaperones and as regulators of different signaling pathways. Both extracellular Trx1 and Prdx1 are known to have pro-inflammatory effects. Our results suggest that preeclampsia might be characterized by different markers of oxidative stress. Changes of the cell surface or intracellular expressions of regulatory molecules, including PRDX1 and TRX1 may be also associated with cell activation and inflammatory conditions.