High mobility group box 1 protein (HMGB-1): a pathogenic role in preeclampsia?

We evaluated whether preeclampsia is associated with elevated circulating levels of High mobility group box 1 protein (HMGB-1), a nuclear protein with proinflammatory effects when released extracellularly. We enrolled 48 women, 32 in third trimester pregnancy (16 with, 16 without preeclampsia), and 16 healthy non pregnant. In the peripheral blood of pregnant women, HMGB-1 concentration was assessed serially, before and after delivery. With or without preeclampsia, third trimester pregnancy was associated with elevated levels of HMGB-1. This elevation is exaggerated in preeclampsia. The source of HMGB-1 observed in these conditions is likely to involve tissues other than the placenta itself.

PP125. High mobility group box 1 protein (HMGB1): A pathogenic role in preeclampsia?

INTRODUCTION: A central pathogenic mechanism of preeclampsia is believed to be the production by the hypoxic placenta of various mediators which promote inflammation and oxidative stress when released into the maternal circulation. The high mobility group box 1 protein (HMGB1) is a ubiquitous nuclear protein. In conditions of hypoxic cellular stress or necrosis, HMGB1 is released into the extracellular milieu. Extracellular HMGB1 has proinflammatory effects, due to the engagement of various cell membrane receptors, notably the receptor for advanced glycation products (RAGE). OBJECTIVES: In preeclampsia, there is evidence for activation of RAGE, and enhanced amounts of HMGB1 have also been demonstrated in the placenta and amniotic fluid, but not, so far, in maternal blood. We hypothesize therefore that, in preeclampsia, the concentration of HMGB1 is abnormally high in maternal blood. METHODS: We enrolled 16 women in third trimester pregnancy and suffering from preeclampsia (blood pressure > 140/90mmHg with significant proteinuria), 16 women with normal pregnancies who were matched pairwise with the former for BMI and gestation week, and 16 non pregnant healthy women, matched for age with the other two groups. HMGB1 was assessed in peripheral blood with a commercial ELISA kit. The variance between the three groups was appreciated using an ANOVA analysis. Significance was considered for a probability value of < 0.5. RESULTS: The median [interquartile range] HMGB1 concentrations (in ng/mL) were 2.1 [1.1-3.2] in preeclamptic pregnancies, 1.1 [1.0-1.2] in normal pregnancies (p<0.05 vs preeclamptic group), and 0.6 [0.5-0.8] in non pregnant women (p<0.01 vs both other groups). CONCLUSION: In third trimester pregnancy, the presence of preeclampsia is associated with an approximately two-fold increase of HMGB1 concentration in maternal peripheral blood. Considering its known proinflammatory effects, HMGB1 could be one mediator responsible for the maternal manifestations of preeclampsia.

[Hypertension in pregnancy]. / Hypertension et grossesse.

Hypertension in pregnancy Hypertension in pregnancy, whether chronic or recently diagnosed, is always a matter of concern for the general practitioner or the obstetrician. Even if this situation often evolves favorably, and although a "wait and see" attitude may be preferred to an aggressive one in such cases, one should also be aware of how dramatic the outcome may also be. As a matter of fact, what is considered as one of the most frequent complications of pregnancy can run out of control, a possibility which shouldn't be dismissed. In this article, we shall discuss the various strategies for managing this disorder.