tissue damage, and vaso-constriction, typical findings inpreeclampsia.

Objective: To study alpha-1-microglobulin (A1M), anendogenous radical scavenger and heme-binder, as a poten-tial treatment for preeclampsia using the pregnant ewe pre-eclampsia model. Free Hb and heme are known to take partin the pathology of this model and therefor well suited forevaluation of recombinant A1M as a therapy.

Methods: 11 pregnant ewes, at gestational age 125–131days, were acclimatized for 36 h and then starved foranother 36 h to induce preeclampsia symptoms. At the endof starvation period, they were treated either with placebo(n = 6) or A1M injections (n = 5). After injections, food wasre-introduced and ewes further followed for 72 h. The eweswere sacrificed the 6th day after beginning of acclimatiza-tion. Throughout the 6 days, the animals were monitoredfor blood pressure and different blood and urine parameters.Whole blood, kidney and placenta tissue samples were col-lected from the ewes. Gene expression analysis, blood anal-ysis, histology and electron microscopy were used toevaluate the therapeutic effects of A1M.

Results: Starvation increased the amount of free heme inthe blood. The ultrastructure of the placenta and kidneywere damaged in a way similar to what previously havebeen described for PE. The glomeruli and the tubuli weredamaged which was reflected by increased Ficol clearanceand increased plasma creatinine levels. Treatment withA1M significantly normalized the kidney functions. Themost profound changes on gene expression level were foundin white blood cells in the starved animals. Starvationdecreases mRNA expression for anti-oxidants such as CAT(P = 0.04), SOD1 (P = 0.008), SOD2 (1.8-fold) as well as angio-genetic factors such as VEGF (P = 0.02) and HGF (1.6-fold).A1M treatment rescued the decreased expression of SOD2(P = 0.04) and HGF (2-fold).

Conclusion: A1M is well tolerated and shows high poten-tial as a treatment for PE-like symptoms in the pregnantewe model for PE.

doi:10.1016/j.preghy.2013.04.038

PP011. Placental expression of the major protein com-ponents of caveolae, eNOS and iNOS in pre-eclampsiaHentschke Marta, Smith-Jackson Kate, Poli-de-FigueiredoCarlos E., Costa Bartira E.P., Kurlak Lesia O., Pipkin FionaBroughton, Czajka Anna, Mistry Hiten D.

Introduction: Caveolins and Cavins are the major proteincomponents of caveolae and regulate many cardiovascularfunctions. Caveolin-1 inhibits eNOS activity. The possibleregulation of vascular reactivity/blood pressure by the cave-olae are of interest in relation to pre-eclampsia (PE). Wehypothesised that expression of Caveolin/Cavin genes wouldbe reduced, paralleling the up-regulated eNOS in PE com-pared to normotensive controls (NC).

Objectives: To analyse the placental mRNA expression ofCaveolins1–3 and, Cavins1–4, eNOS and iNOS; and proteinof caveolin-1, cavin-1 and eNOS in NC and PE placentae fromWhite European women.

Methods: Following ethical approval and informed writtenconsent, placental biopsies were taken midway between thecord and periphery, avoiding infarcts, from 24 NC and 23 PEpatients. Gene expression was measured by qRT-PCR. Pro-tein localization was identified by immunohistochemistryand expression semi-quantitatively assessed.

Results: Results of mRNA/proteins are shown on tablebelow. Protein expression was localised to the cytotropho-blast and syncytiotrophoblast. No differences were foundfor any other gene/protein.

Conclusion: As well as their known effects on eNOSexpression, caveolae mediate internalisation of numeroushormone receptors, thus potentially changing pressor anddepressor responsiveness. This is the first time that struc-tural determinants of caveolae have been studied in NCand PE pregnancy.

Funding: Tommy’s, CAPES.

PP011. Table 1.

Median [IQR] NC PE P

Cavin-1 2.2 [1.7, 3.7] 1.4 [0.7, 1.9] <0.0001

Cavin-2 0.4 [0.1, 1.6] 0.07 [0.04,0.2] 0.003

Cavin-3 0.5 [0.2,1.6] 0.2 [0.08, 0.2] 0.025

Caveolin-1 7.3 [3.8, 15.9] 5.2 [1.6, 8.5] 0.007

eNOS 1.1 [0.3, 5.2] 5.2 [1.6, 8.5] 0.045

Caveolin-1 IHC 0.9 [0.8,0.9] 0.8 [0.7,0.8] 0.001

doi:10.1016/j.preghy.2013.04.039

PP012. Abnormal vascular umbilical cord morphology invascular-related pregnancy complications

Herzog Emilie, Reijnierse Anniek, Krijger Ronald de,Steegers Eric, Steegers-Theunissen Régine

Background: Preeclampsia (PE), foetal growth restriction(FGR) and preterm birth (PTB) are associated with anincreased risk on the development of cardiovascular diseasein offspring. Abnormal programming of the embryonic andextra-embryonic vasculature may be involved. The umbilicalcord could be a good model for studying foetal vasculardevelopment.

Objectives: We examined the morphology of the umbilicalcord vasculature in complicated (PE, FGR, PTB) and uncom-plicated pregnancies.

Methods: In a case-control study, we included 105patients consisting of PE (n = 31), FGR (n = 26), PTB (n = 24)and controls (n = 24). Macroscopic measurements wereperformed and tissue samples were formalin-fixed within1 hour after birth, for microscopic analysis of digitised par-affin sections.

Results: The macroscopic evaluation showed shorterumbilical cords in PE than in controls. Microscopic measure-ments revealed a smaller total cord area in all complicatedpregnancies compared to controls. The artery wall areawas smaller in PE and IUGR, and a smaller vein wall areawas present in PE only, compared to controls. The percent-age of elastic fibres in the vein was lower in PE and IUGRthan in controls (Table 1).

Poster Presentations / Pregnancy Hypertension: An International Journal of Women’s Cardiovascular Health 3 (2013) 67–99 71

Conclusion: Our study demonstrates umbilical cord vascu-lar abnormalities in PE, FGR and PTB, suggesting early vascu-lar damage. Future studies should focus on similar structuralchanges in foetal vasculature and associations with cardio-vascular disease in later life.

doi:10.1016/j.preghy.2013.04.040

PP013. Single nucleotide polymorphisms of the maternalcystathionine-b-synthase gene are associated with pre-eclampsia (PE)Holwerda Kim, Weedon-Fekjær Susanne, Staff Annetine,

Nolte Ilja, Goor Harry van, Lely Titia, Faas Marijke

Introduction: Cystathionine-b-synthase (CBS) producesthe vasodilatory and anti-inflammatory hydrogen sulfide(H2S) by conversion of homocysteine (Hcy). H2S is involvedin placental vascular tone regulation. Previously, we showedthat woman with PE have hyperhomocysteinemia anddecreased placental CBS gene expression.

Objectives: Aberrant CBS gene expression may play a rolein hyperhomocysteinemia and decreased H2S and could beinvolved in pathogenesis of PE. We studied whether thepresence of CBS single nucleotide polymorphisms (SNPs) isassociated with the development of PE.

Methods: Six CBS SNPs (rs12329764, rs2851391,rs234713, rs234706, rs1789953, rs11203172) were geno-typed in 99 controls, 60 severe, and 39 mild PE cases. Severeand mild PE cases were additionally subdivided into late-(>34 weeks) and early-onset (<34 weeks) PE. The associationof the alleles with development PE was tested with logisticregression.

Results: Two of the six SNPs are associated with PE. Theminor allele for rs11203172 reduces the risk for developingsevere PE (OR[95% CI] = 0.54[0.21–0.94], p = 0.023). Theminor allele for rs234706, which is associated with lowHcy, increased the risk to develop mild, late-onset PE(2.10[1.15–3.85], p = 0.016).

Conclusion: SNPs in the CBS gene are associated with riskof developing PE. Within the CBS gene, SNPs associated withboth a decreased and an increased risk to develop PE were

found. Altered effectiveness of CBS may affect PE throughdecreased H2S production or Hcy accumulation.

doi:10.1016/j.preghy.2013.04.041

PP014. A pioneer explore of PTZ-induced eclampsia inpreeclampsia ratsHuang Qian, Liu Huishu, Hu Bihui, Ye Yuanjuan

Introduction: Eclampsia is the most serious state of hyper-tensive disorder in pregnancy, but the pathogenesis ofeclampsia seizures is poorly understood.

Objectives: An eclampsia animal model was developed byPTZ injection on preeclampsia rats.

Method: Rats received endotoxin (1.0 lg/kg body weight)form tail vein in an hour on GD14 to build the preeclampsia(PE) model. PTZ i.p injection were given to PE rats on GD16,17, 18 to induce seizures and build an eclampsia model. Allexperiment rats were divided into three groups, PE, normal,pregnant (P), non-pregnant (NP) group (n = 18 in each group).Each group gave two doses of PTZ (40 or 35 mg/kg) as sub-groups. Blood pressure, urinary albumin, biochemicalindexes (AST, ALT, SCr, Urea) were measured. Seizure sever-ity was defined by Racine’ standard and seizure time wererecorded.

Results: PTZ-induced eclampsia shows a increasing bloodpressure, urinary albumin, liver function damage and differentstages of seizures. The latency of seizure in PE rats with 40 mg/kg PTZ is obviously shortened when compared with the P andNP group (p < 0.05) and the duration is prolonged (p < 0.05).The same trend is still existence at the low dose of PTZ injec-tion. Rate of tonic-clonic seizures is elevated in PE and Pgroup when compared with NP group, but nonsignificantly.

Conclusion: We use 40 mg/kg PTZ to endotoxin inducedpreeclampsia model to build an eclampsia model, whichmimicked the multiple organ function disorder in humaneclampsia. Meanwhile, we found the PE status maydecreases threshold for PTZ induced-seizures.

doi:10.1016/j.preghy.2013.04.042

PP012. Table 1. Umbilical cord morphology.

PE (n = 31) FGR (n = 26) PTB (n = 24) Controls (n = 24) Overall P-value

Macroscopy

Length (cm) 43.25⁄ 50.09 46.08 50.94 P = 0.006

(19–75) (27–69) (20–64) (24–86)

Microscopy

Total cord area (mm2) 74.06⁄ 68.65⁄ 85.88⁄ 112.63 P < 0.001

(37.84–131.21) (31.87–145.35) (55.80–109.69) (64.89–182.60)

Vein wall area (mm2) 4.39⁄ 5.55 6.80 7.20 P = 0.020

(1.66–17.43) (1.63–10.45) (2.36–13.69) (4.27–13.12)

Artery wall area (mm2) 2.29⁄ 2.52⁄ 3.11 3.46 P < 0.001

(1.62–3.44) (1.62–3.79) (1.93–5.69) (2.45–5.26)

Vein elastic fibres (%) 7.18⁄ 7.32⁄ 7.53 8.99 P = 0.022

(2.88–13.85) (4.16–12.37) (4.85–16.23) (5.59–17.41)

ANOVA, mean (range).⁄ P < 0.05 compared to controls.

72 Poster Presentations / Pregnancy Hypertension: An International Journal of Women’s Cardiovascular Health 3 (2013) 67–99