Marta Ribeiro Hentschke

Is the atherosclerotic phenotype of preeclamptic placentas due to altered lipoprotein concentrations and placental lipoprotein receptors? Role of a small-for-gestational-age phenotype.

Atherosis of spiral arteries in uteroplacental beds from preeclamptic women resemble those of atherosclerosis, characterized by increased plasma lipids and lipoproteins. We hypothesized that: 1) lipoprotein receptors/transporters in the placenta would be upregulated in preeclampsia, associated with increased maternal and fetal lipoprotein concentrations; and 2) expression of these would be reduced in preeclamptic placentae from women delivering small-for-gestational-age (SGA) infants. Placental biopsies and maternal and umbilical serum samples were taken from 27 normotensive and 24 preeclamptic women. Maternal/umbilical cord serum LDL, HDL, total cholesterol, and triglycerides were measured. Placental mRNA expression of lipoprotein receptors/transporters were quantified using quantitative RT-PCR. Protein localization/expression of LDL receptor-related protein 1 (LRP-1) in the preeclamptic placentae with/without SGA was measured by immunohistochemistry. Placental mRNA expression of all genes except paraoxonase-1 (PON-1), microsomal triglyceride transfer protein (MTTP), and protein disulfide isomerase family A member 2 (PDIA2) were observed. No differences for any lipoprotein receptors/transporters were found between groups; however, in the preeclamptic group placental LRP-1 expression was lower in SGA delivering mothers (n = 7; P = 0.036). LRP-1 protein was localized around fetal vessels and Hofbauer cells. This is the first detailed study of maternal/fetal lipoprotein concentrations and placental lipoprotein receptor mRNA expression in normotensive and preeclamptic pregnancies. These findings do not support a role of altered lipid metabolism in preeclampsia, but may be involved in fetal growth.

Endocan-1 concentrations in maternal and fetal plasma and placentae in pre-eclampsia in the third trimester of pregnancy.

INTRODUCTION Endocan-1 has been proposed as a possible biomarker and predictor of vascular endothelial related pathologies. Thus, we hypothesised that Endocan-1 levels would be up-regulated in maternal plasma and placentae from women with pre-eclampsia. The aim of our study was to compare Endocan-1 concentrations in maternal/fetal plasma and placentae from normotensive and pre-eclamptic pregnancies. METHODS Observational and case-controlled study, at the São Lucas Hospital, Brazil. Placental biopsies, maternal/umbilical venous (fetal) plasma were taken from 67 normotensive and 50 pre-eclamptic women. Endocan-1 levels were quantified using MagPlex(TH)-C and analysed by Analysis of Covariance and Pearson correlation. The null hypothesis was rejected at p<0.05. RESULTS Higher levels of Endocan-1 were found in maternal plasma in the pre-eclamptic group (mean ratio=1.49; 95% confidence interval: 1.19-1.85, p=0.001), with a moderate effect size (Cohens D=0.84). Placental Endocan-1 levels (μg/g) were lower in pre-eclampsia (1.52 [1.10, 2.40] vs. 2.24 [1.32, 3.75], p=0.033) and fetal Endocan-1 concentration (ng/ml) did not show any difference between groups (3.10 [2.60, 4.54] vs. 2.91 [2.20, 3.66] p=0.085). In addition, an up-regulation of maternal plasma Endocan-1 in the pre-eclamptic group was observed when stratified in relation to gestational age, systolic blood pressure and proteinuria (p<0.05, for all). Furthermore, a positive correlation between Endocan-1 concentration in maternal vs. fetal plasma was also found (r=0.258, p=0.015). For the matched samples, a negative correlation between Endocan-1 in maternal/fetal plasma with birthweights, placental weights and gestational age at delivery was observed (p<0.05 for all). DISCUSSION Endocan-1 is increased in women with pre-eclampsia for all strata, which highlight the importance of this molecule as a possible biomarker. The negative correlations between Endocan-1 and clinical data suggest that this molecule may also be involved with prematurity and low birth weight, which warrants further investigations.

Increased levels of the soluble receptor of Interleukin-6 in patients with preeclampsia compared to normotensive pregnant women

AIMS: To compare Interleukin-6 soluble receptor (IL-6sR) plasmatic levels between normotensive pregnant controls and preeclamptic women. METHODS: Maternal blood samples were collected before delivery from 21 patients with preeclampsia and 39 normotensive pregnant controls. Samples were stored at -80°C until laboratory assay. IL-6sR was measured by ELISA enzyme immunoassay. To compare groups Students t test was used. Results with P less than 0.05 were considered significant. RESULTS: Data from preeclampsia and normotensive pregnant controls were respectively: maternal age 22.3±4.8 vs 26.0±3.7 years (P=0.06); gestational age 32.7±5.8 vs 40.1±0.8 weeks (P=0.01); systolic blood pressure 143.0±2.2 vs 118.8±3.1 mmHg (P=0.01); diastolic blood pressure 112.5±4.0 vs 77.2±10.2 mmHg (P=0.01); uric acid 5.87±1.10 vs 4.57±0.12 mg/dL (P=0.02); creatinine 0.82±0.12 vs 0.73±0.09 mg/dL (P=0.01); birth weight 2130.7±839.3 vs 3555.0±261.0 g (P=0.01); placental weight 621.3±167.0 vs 796.3±154.2 g (P=0,05). Proteinuria over creatininuria ratio in the preeclampsia group was 2.40±1.31. The concentration of IL-6sR (ng/dL) was 28.7±10.8 in preeclampsia vs 16.5±6.4 in normotensive pregnant controls (P=0.01). CONCLUSIONS: These results show an increased plasma levels of IL-6sRin patients with preeclampsia compared to normotensive pregnant women. More studies are necessary to clarify the pathophysiology of this entity, including the analysis of other cytokines linked to this receptor, due to the fact that they can be the key for the systemic inflammatory response that occurs in these patients and therefore for their treatment.

PP040. Expression of RANTES (CCL5) in maternal plasma, fetal plasma and placenta in pre-eclampsia and normotensive controls

INTRODUCTION Studies have shown pre-eclampsia (PE) as an exacerbation of gestational inflammatory process. RANTES (Regulated upon Activation, Normal T-cell Expressed, and Secreted)/CCL5 is a chemokine, which is involved in chronic inflammation by the recruitment of inflammatory cells. It is secreted by many cell types such as endothelial cells, smooth muscle cells, macrophages, platelets and activated T-cells. Thus we hypothesized that RANTES expression is altered in PE and may be different in gestational tissues (maternal plasma, fetal plasma and placenta). OBJECTIVES The purpose of the study is to analyze the expression of RANTES (CCL5) in three different tissues: maternal plasma, fetal plasma and placenta, in PE and normotensive controls (NC). METHODS PE was diagnosed by the National High Blood Pressure Education Program Working Group Report on High Blood Pressure in Pregnancy guidelines. The patients were assisted in the São Lucas Hospital from PUCRS, Porto Alegre, Brazil. Following ethical approval and informed written consent, maternal and umbilical plasma and placental biopsies were taken from 33 PE and 35 NC. Samples were centrifuged immediately after blood collection and plasma was stored at -80°C until assay. Placental Biopsies were taken midway between the cord and periphery, from the central region of cotyledons and were stored as well. RANTES expression was made by the ELISA test, in duplicates. They were also analyzed in each group: maternal age, maternal parity, gestational age on delivery, glucose, body mass index, proteinúria creatinuria ratio, systolic blood pressure (SBP), diastolic blood pressure (DBP), delivery method, birth weight, placental weight and Apgar index in 1st and 5th minute. RESULTS Maternal age at the time of blood collection was not significantly different between the two groups. The women with preeclampsia delivered earlier and had smaller babies compared with the controls. Significant associations between groups (p<0.001) were seen in SBP, DBP, birth weight and delivery method. RANTES was increased in maternal plasma and placenta in patients with PE and decreased in fetus plasma in the same group (p<0.001). CONCLUSION In this study, we have shown that RANTES expression in maternal plasma and placenta tissues, in women with established pre-eclampsia, is higher than in gestation-matched women with a healthy pregnancy. It confirms the hypotheses that physiology of PE is associated with an increase of normal gestational inflammatory process. However in fetus tissue, the inflammatory chemokine is decreased in PE women. FUNDING CAPES Foundation, Ministry of Education of Brazil, Brasília - DF 70040-020, Brazil.

Is there any relationship between ABO/Rh blood group and patients with pre-eclampsia?

OBJECTIVES The purpose of the present study was to evaluate the association between pre-eclampsia and blood groups in a group of pregnant women hospitalized in a University Hospital in Porto Alegre, Brazil - Hospital São Lucas (HSL)/PUCRS. STUDY DESIGN Our sample consisted of 10,040 pregnant women admitted to the maternity department of HSL between 2005 and 2010. The patients were reviewed retrospectively for inclusion. Medical records of 414 women were diagnosed as preeclampsia/eclampsia and 9611 women were identified to the control group. The patients were divided into two groups: the group with preeclampsia/eclampsia and the control group, and their blood groups were considered. Data were analyzed using SPSS for Windows version 17.0. Categorical data were summarized by counts and percentages, with the statistical significance evaluated by the Chi-square test. The null hypothesis was rejected when p<0.05. MAIN OUTCOME MEASURES Maternal parameters were compared between control group and pre-eclampsia, respectively, Systolic Blood Pressure (117±19.98 vs. 165±19.99); Diastolic Blood Pressure (73±14.23 vs. 106±14.24) and maternal weight at booking (73±33 vs. 83±33). For all data: mean+SD; p<0.05. In relation to blood groups, firstly they were stratified by Rh and ABO phenotypes, separately. After that the groups were put together. RESULTS No differences in blood group distribution were observed between controls and pre-eclampsia for any analysis. (p>0.05). CONCLUSIONS When we adopted stricter criteria for pre-eclampsia and a large sample from the same region we noted that the results did not show any association between blood groups and the development of pre-eclampsia.

PP011. Placental expression of the major protein components of caveolae, eNOS and iNOS in pre-eclampsia

INTRODUCTION Caveolins and Cavins are the major protein components of caveolae and regulate many cardiovascular functions. Caveolin-1 inhibits eNOS activity. The possible regulation of vascular reactivity/blood pressure by the caveolae are of interest in relation to pre-eclampsia (PE). We hypothesised that expression of Caveolin/Cavin genes would be reduced, paralleling the up-regulated eNOS in PE compared to normotensive controls (NC). OBJECTIVES To analyse the placental mRNA expression of Caveolins1-3 and, Cavins1-4, eNOS and iNOS; and protein of caveolin-1, cavin-1 and eNOS in NC and PE placentae from White European women. METHODS Following ethical approval and informed written consent, placental biopsies were taken midway between the cord and periphery, avoiding infarcts, from 24 NC and 23 PE patients. Gene expression was measured by qRT-PCR. Protein localization was identified by immunohistochemistry and expression semi-quantitatively assessed. RESULTS Results of mRNA/proteins are shown on table below. Protein expression was localised to the cytotrophoblast and syncytiotrophoblast. No differences were found for any other gene/protein. CONCLUSION As well as their known effects on eNOS expression, caveolae mediate internalisation of numerous hormone receptors, thus potentially changing pressor and depressor responsiveness. This is the first time that structural determinants of caveolae have been studied in NC and PE pregnancy. FUNDING Tommys, CAPES.

Negative Correlation between Placental Growth Factor and Endocan-1 in Women with Preeclampsia

OBJECTIVE  To analyze endocan-1, a biomarker of vascular endothelial related pathologies, and the placental growth factor (PlGF), an angiogenic factor and a placental dysfunction marker in patients with preeclampsia (PE). METHODS  Case-control study conducted at Hospital São Lucas, in the city of Porto Alegre, Brazil. Endocan-1 and PlGF levels were quantified in the maternal plasma using the MagPlexTH-C microsphere system (MAGPIX System, Luminex, Austin, Texas, US) and evaluated through analysis of covariance (ANCOVA) and adjusted by body mass index (BMI), gestational age and maternal age. To estimate the difference between the groups, the mean ratio (MR) and the 95% confidence interval (95%CI) were calculated. The Pearson correlation test was used to establish any association between endocan-1 and PlGF levels. The null hypothesis was rejected when p < 0.05. RESULTS  The group of patients was composed by normotensive (n = 67) patients and patients with PE (n = 50). A negative correlation between endocan-1 and the PlGF was noted in the entire normotensive group (linear correlation coefficient [r] = -0.605; p < 0.001), as well as in the PE group (r = -0.545; p < 0.001). CONCLUSION  Endocan-1 levels are increased in patients with PE, and are inversely correlated with PlGF levels. We suggest that it is important to analyze angiogenic and proinflammatory molecules concomitantly in women with PE to better understand the pathophysiology of the disease. Both molecules are strong candidates for PE biomarkers, and future studies will examine any mechanisms connecting these factors in PE.

Reversible hemianopsia in postpartum due to posterior reversible encephalopathy syndrome in pregnant with late eclampsia

OBJECTIVES To describe a case of Posterior Reversible Encephalopathy Syndrome diagnosed in pregnant women with late-eclampsia, as well as its clinical management. CASE DESCRIPTION A 34 years old patient in her third pregnancy had started with high blood pressure levels during labor; after eleven days postpartum, she presented a decreased right visual acuity; subsequently one episode of seizure followed by partial loss of vision in the right eye. After conducting tests and ruled out stroke, the patient was diagnosed as Posterior Reversible Encephalopathy Syndrome (PRES). Established the clinical management of seizures and hypertensive crisis, there was complete remission of symptoms and reversal of the initial clinical picture. CONCLUSION Once properly diagnosed and treated, the Posterior Reversible Encephalopathy Syndrome can present satisfactory progress, especially when associated with an acutely triggered factor, as eclampsia.

Takayasu Arteritis diagnosed during puerperium in a woman with pregnancy-induced hypertension: Case report

AIMS: To describe a case of Takayasu arteritis diagnosed during the early postpartum period, demonstrating the importance of proper blood pressure measurement for the diagnosis of gestational hypertension. CASE DESCRIPTION: A 40 year old woman in her fourth pregnancy, with gestational age of 36 weeks and three days, was hospitalized for high-risk pregnancy due to chronic hypertension. During hospitalization, difference in blood pressure levels and pulse asymmetry between the upper limbs were observed. In the postpartum the patient underwent carotid Doppler ultrasound, which showed occlusion of the left common carotid artery and left subclavian artery, leading to the diagnosis of Takayasu arteritis. CONCLUSIONS: Early diagnosis of Takayasu arteritis is difficult because initial manifestations are nonspecific and symptoms are mild. However, a careful physical examination may reveal signs that raise suspicion and warrant further investigation, which may prevent a negative outcome, especially during pregnancy.

OS080. Maternal and fetal lipoprotein concentrations and expression of placental lipoprotein transporters in pre-eclampsia and normotensive controls.

OS080. Maternal and fetal lipoprotein concentrations and expression of placental lipoprotein transporters in preeclampsia and normotensive controls M.R. Hentschke , C.E. Poli-de-Figueiredo , L.O. Kurlak , P.J. Williams , H.D. Mistry 2 (Nephrology, School of Medicine, Pontificia Universidade Catolica do Rio Grande do Sul, Porto Alegre, Brazil, Women’s Health, King’s College London, United Kingdom, Obstetrics & Gynaecology, University of Nottingham, Nottingham, United Kingdom, Human Genetics Research Group, University of Nottingham, Nottingham, United Kingdom)