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Abstracts / Placenta 34 (2013) A1–A99 A41

Conclusion: Free HbF causes acute vasoconstriction of the fetoplacentalvasculature by binding NO and disrupting placental endothelialmorphology. HbF levels in fetal blood warrant further investigation innormal and pathological pregnancies.

http://dx.doi.org/10.1016/j.placenta.2013.06.121

P1.85.ABSTRACT WITHDRAWN

HTTP://DX.DOI.ORG/10.1016/J.PLACENTA.2013.06.122

P1.86.MATERNAL SERUM LEVELS OF FGL2 AS SCREENING TOOL FORPREECLAMPSIA

Julien Yockell-Lelievre 1, Barbara Vanderhyden 1,2, Andree Gruslin 1,3

1Ottawa Hospital Research Institute, Ottawa, ON, Canada; 2Department ofCellular and Molecular Medicine, University of Ottawa, Ottawa, ON,Canada; 3Department of Obstetrics and Gynecology, The Ottawa Hospital,Ottawa, ON, Canada

Background: Multiple factors are involved in the development of pre-eclampsia (PE), making its prediction complex. Abnormal trophoblast inva-sion, oxygen disruption, anti-angiogenic response and an altered immuneresponse have all been linked to this syndrome. Fibrinogen-like protein 2(FGL2) is a tetrameric cell-surface prothrombinase previously linked to spon-taneousabortions throughaprocessof leukocyteactivation. Itwasshowntobehighly expressed in trophoblasts, and its ability to induce coagulation sug-gested it might play a role in the pathogenesis of PE. It was demonstrated thatFGL2 deficient mice were resistant to lipopolysaccharides (LPS)-inducedabortions but that these same mice had smaller litters under normal condi-tions. This observation could be explained by the fact that the soluble form ofFGL2, possesses immunosuppressive activity by binding to the Fc gamma re-ceptor (FcgammaR)IIB expressed on the surface of antigen presenting cells.Hypothesis:Given the role of FGL2 in coagulation and immunemodulation,we postulate that in preeclampsia, FGL2 is differentially secreted into thematernal circulation, and therefore could be used as an early prediction tool.Methods: First trimester serum samples from the OaK (Ottawa andKingston) cohort were analysed. The samples from mothers who devel-oped preeclampsia (n¼13) were compared to samples from healthypregnancies (n¼38). FGL2 was quantified by ELISA and Western blot.Results:While no difference in concentrations of total FGL2 were found byELISA between PE cases and healthy controls, Western blots indicated thatthe amount of monomeric FGL2 was significantly lower in the serum ofwomen who eventually developed preeclampsia (4.4 fold, P<0.05).Conclusion: Since it has been previously reported that monomeric FGL2has enhanced immunosuppressive activity in comparison to the oligo-meric FGL2, our results suggest that high circulating levels of monomericFGL2 could have a protective effect against PE.


P1.87.ANTI-INFLAMMATORY EFFECT OF LOW MOLECULAR WEIGHT HEPARIN(LMWH) IS MEDIATED BY PLACENTAL HIGH MOBILITY GROUP BOX 1(HMGB1) MODULATION: NEW THERAPEUTIC PERSPECTIVES FORPREECLAMPSIA

Cristian Zenerino 1, Anna Maria Nuzzo 1, Alessandra Zicari 2,Domenica Giuffrida 1, Tullia Todros 1, Alessandro Rolfo 1

1Dept. of Surgical Sciences, University of Turin, Turin, Italy; 2Dept. ofExperimental Medicine, University La Sapienza, Rome, Italy

Objectives: Preeclampsia (PE) is a severe pregnancy-related syndromecharacterized by exacerbated placental inflammation. LMWH is widelyused during PE since several trials described its anti-inflammatory effect.Nevertheless, LMWH mechanisms of action on the placental tissue arestill unclear. HMGB1 is a transcription factor with an extracellular cyto-kine-like function able to induce pro-inflammatory TNFa and IL-6 mol-ecules. LMWH binds to HMGB1 in-vitro, thus changing its structuralconformation and inhibiting its activity. Since HMGB1 has been previ-ously found up-regulated in PE, in the present study we investigatedLMWH's modulation of HMGB1 and its targets TNFa and IL-6 in theplacental tissue.Methods: Twenty-eight normal placental villous explants were treated for48h with different concentrations of LMWH (Parnaparin 50U, 5U, 0.5U).HMGB1, TNFa and IL-6 mRNA expression was assessed by Real Time PCRwhile HMGB1 protein expression was analyzed by Western Blot analysis.Results: While 50U and 5U were toxic for our in-vitro model, we reportedsignificantly decreased gene expression levels of HMGB1, TNFa and IL-6 inplacental villous explants treated with LMWH 0.5U vs untreated controls.In contrast, HMGB1 protein levels were increased in LMWH 0.5U explantscompared to controls.Conclusion: Herein, we described a direct effect of LMWH onplacental HMGB1 modulation. Indeed, HMGB1 protein increaseaccompanied by decreased TNFa and IL-6 expression in LMWH villousexplants confirm the anti-inflammatory effect of heparin and suggestthat it is mediated by structural modifications of HMGB1 able topromote its accumulation and to inhibit its function. Further in-vestigations are required.


P1.88.HEPCIDIN EXPRESSION IN PLACENTAE FROM PREECLAMPTIC PREG-NANCIES WITH OR WITHOUT FETAL GROWTH RESTRICTION

Anna Maria Nuzzo, Alessandro Rolfo, Simona Cardaropoli,Ettore Piccoli, Annalisa Piazzese, Tullia Todros

Dept. of Surgical Sciences, University of Turin, Turin, Italy

Objectives: Hepcidin is a peptide that acts as negative regulator ofcellular iron efflux, thus exerting a protective effect against oxidativestress. Hepcidin is negatively regulated by hypoxia via HypoxiaInducible Factror-1 (HIF-1). Increased placental hypoxia/oxidativestress and HIF-1 expression are key hallmarks of preeclamptic (PE)pregnancies affected by Fetal Growth Restriction (FGR). Nothing isknown about the role of hepcidin during physiological and patholog-ical placentation. In the present study, we characterized placentalhepcidin expression in normal and in PE pregnancies complicated ornot by FGR.Methods: Placentae from PE with appropriate for gestational age fetuses(PE-AGA, n¼7), PE with FGR (n¼10) and control pregnant women (n¼20)were collected. Placental biopsies were processed for mRNA and proteinisolation. Hepcidin gene and protein expressions were evaluated usingReal Time PCR and competitive Enzyme-Linked ImmunoSorbent (ELISA)respectively.Results:We found decreased hepcidin mRNA and protein levels in PE-AGAvs controls (1.81 and 1.77 Fold decrease respectively). No differences werefound between PE-FGR and control placentae.Conclusion: Decreased hepcidin in PE-AGA group, characterized by normalplacentation, could be due to other factors than hypoxia/oxidative stress,thus requiring further investigation. Data on PE-FGRgroupmust be carefullyinterpreted since hepcidin is known to decreasewith advancing gestation innormal pregnancy. Indeed, as PE-FGR presented lower gestational agerelative to controls (33�3 vs 39�1 weeks), they should be considered asexpressing less placental hepcidin, possibly due to placental hypoxia.


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