Potential Biomarkers of Preeclampsia: Inverse Correlation between Hydrogen Peroxide and Nitric Oxide Early in Maternal Circulation and at Term in Placenta of Women with Preeclampsia

Preeclampsia (PE) is a pregnancy-specific disease that has been associated with future cardiovascular disease for the mother and her child. The etiology of PE is unclear but oxidative stress seems to play a major role in endothelial dysfunction and permanent systemic vasoconstriction shown in PE. Hydrogen peroxide (H2O2), a terminal metabolite of the cellular oxidative stress cascade, is also revealed as a component of oxidative ischemia/reperfusion stress in placenta. We were the first to show an increase in the levels of H2O2 in the serum of preeclamptic women at term. H2O2 is already known to reduce the production of NO by increasing the metabolism of arginases. The objective of this study was to investigate a possible correlation between nitric oxide (NO), a potent vasodilator, and H2O2 throughout pregnancy. Thus, we simultaneously assessed the levels of NO and H2O2 in the serum of normal and preeclamptic women at 10-15 and 37-40 weeks of pregnancy, and in placentas at delivery. Our findings showed an inverse correlation between increased levels of H2O2 and decreased levels of NO early in maternal circulation and at term in placenta. This relationship is confirmed by our in vitro experiments which demonstrate that H2O2 inhibits NO synthesis of cytotrophoblasts. In conclusion, our findings highlight an inverse correlation between H2O2 and NO early in maternal circulation and in placenta of women with preeclampsia, paving the way for further studies examining the potential use of NO and H2O2 as biomarkers in the prediction of preeclampsia.