Dataset Information

Low Soluble Syndecan-1 Precedes Preeclampsia.

ABSTRACT:

Introduction

Syndecan-1 (Sdc1; CD138) is a major transmembrane heparan sulfate proteoglycan expressed on the extracellular, luminal surface of epithelial cells and syncytiotrophoblast, thus comprising a major component of the glycocalyx of these cells. The "soluble" (shed) form of Sdc1 has paracrine and autocrine functions and is normally produced in a regulated fashion. We compared plasma soluble Sdc1 concentrations, in relation to placental Sdc1 expression, in uncomplicated (control) and preeclamptic pregnancies.

Methods

We evaluated soluble Sdc1 across uncomplicated pregnancy, and between preeclamptic, gestational hypertensive and control patients at mid-pregnancy (20 weeks) and 3rd trimester by ELISA. Placental expression level of Sdc1 was compared between groups in relation to pre-delivery plasma soluble Sdc1. Participants were recruited from Magee-Womens Hospital.

Results

In uncomplicated pregnancy, plasma soluble Sdc1 rose significantly in the 1st trimester, and reached an approximate 50-fold increase at term compared to post pregnancy levels. Soluble Sdc1 was lower at mid-pregnancy in women who later developed preeclampsia (P<0.05), but not gestational hypertension, compared to controls, and remained lower at late pregnancy in preeclampsia (P<0.01) compared to controls. Sdc1 was prominently expressed on syncytiotrophoblast of microvilli. Syncytiotrophoblast Sdc1 immunostaining intensities, and mRNA content in villous homogenates, were lower in preeclampsia vs. controls (P<0.05). Soluble Sdc1 and Sdc1 immunostaining scores were inversely associated with systolic blood pressures, and positively correlated with infant birth weight percentile.

Conclusion

Soluble Sdc1 is significantly lower before the clinical onset of preeclampsia, with reduced expression of Sdc1 in the delivered placenta, suggesting a role for glycocalyx disturbance in preeclampsia pathophysiology.

SUBMITTER: Gandley RE

PROVIDER: S-EPMC4907460 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Low Soluble Syndecan-1 Precedes Preeclampsia.

Gandley Robin E RE Althouse Andrew A Jeyabalan Arundhathi A Bregand-White Julia M JM McGonigal Stacy S Myerski Ashley C AC Gallaher Marcia M Powers Robert W RW Hubel Carl A CA

PloS one 20160614 6

<h4>Introduction</h4>Syndecan-1 (Sdc1; CD138) is a major transmembrane heparan sulfate proteoglycan expressed on the extracellular, luminal surface of epithelial cells and syncytiotrophoblast, thus comprising a major component of the glycocalyx of these cells. The "soluble" (shed) form of Sdc1 has paracrine and autocrine functions and is normally produced in a regulated fashion. We compared plasma soluble Sdc1 concentrations, in relation to placental Sdc1 expression, in uncomplicated (control) a ...[more]

PMID: 27299886

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Project description:Preeclampsia is characterized by maternal systemic anti-angiogenic and pro-inflammatory states. Syndecan-1 is a cell surface proteoglycan expressed by the syncytiotrophoblast, which plays an important role in angiogenesis and resolution of inflammation. Our aim was to examine placental syndecan-1 expression in preeclampsia with or without hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome. Placentas were obtained from women in the following groups: (1) late-onset preeclampsia (n = 8); (2) early-onset preeclampsia without (n = 7) and (3) with HELLP syndrome (n = 8); (4) preterm controls (n = 5); and (5) term controls (n = 9). Tissue microarrays (TMAs) were constructed from paraffin-embedded placentas. TMA slides were immunostained for syndecan-1 and evaluated using microscopy, virtual microscopy, and semi-automated image analysis. Maternal sera from patients with preeclampsia (n = 49) and controls (n = 32) were immunoassayed for syndecan-1. BeWo cells were treated with Forskolin or Latrunculin B or kept in ischemic conditions. SDC1 expression and syndecan-1 production were investigated with qRT-PCR, confocal microscopy, and immunoassays. Syndecan-1 was localized to the syncytiotrophoblast apical membrane in normal placentas. Syndecan-1 immunoscores were higher in late-onset preeclampsia (p = 0.0001) and early-onset preeclampsia with or without HELLP syndrome (p = 0.02 for both) than in controls. Maternal serum syndecan-1 concentration was lower in preeclampsia (median, 673 ng/ml; interquartile range, 459-1,161 ng/ml) than in controls (1,158 ng/ml; 622-1,480 ng/ml). SDC1 expression and syndecan-1 immunostainings in BeWo cells and syndecan-1 concentrations in supernatants increased during cell differentiation. Disruption of the actin cytoskeleton with Latrunculin B decreased syndecan-1 release, while ischemic conditions increased it. Syncytiotrophoblastic syndecan-1 expression depends on the differentiation of villous trophoblasts, and trophoblastic syndecan-1 release is decreased in preeclampsia and HELLP syndrome. This phenomenon may be related to the disturbed syncytiotrophoblastic cortical actin cytoskeleton and associated with maternal anti-angiogenic and pro-inflammatory states in these syndromes.

Project description:BackgroundThe purpose of this study was to compare plasma soluble endoglin (sEng) levels with standard clinical evaluation or plasma levels of other angiogenic proteins [soluble fms-like tyrosine kinase 1 (sFlt1) and placental growth factor (PlGF)] in predicting short-term adverse maternal and perinatal outcomes in women with suspected preeclampsia presenting prior to 34 weeks.Methods and findingsData from all women presenting at <34 weeks for evaluation of preeclampsia with singleton pregnancies (July 2009-October 2010) were included in this analysis and sEng levels were measured at presentation. Data was analyzed for 170 triage encounters and presented as median {25-75(th) centile}. Thirty-three percent of patients (56 of 170) experienced an adverse outcome. sEng levels (ng/ml) were significantly elevated in patients who subsequently experienced adverse outcomes compared to those who did not (32.3 {18.1, 55.8} vs 4.8 {3.2, 8.6}, p<0.0001). At a 10% false positive rate, sEng had higher detection rates of adverse outcomes than the combination of highest systolic blood pressure, proteinuria and abnormal laboratory tests (80.4 {70.0, 90.8} vs 63.8 {51.4, 76.2}, respectively). Subjects in the highest quartile of sEng were more likely to deliver early compared to those in the lowest quartile (HR: 14.96 95% CI: 8.73-25.62, p<0.0001). Natural log transformed sEng correlated positively with log sFlt1 levels (r = 0.87) and inversely with log PlGF levels (r = -0.79) (p<0.0001 for both). Plasma sEng had comparable area under the curve for prediction of adverse outcomes as measurement of sFlt1/PlGF ratio (0.88 {0.81, 0.95} for sEng versus 0.89 {0.83, 0.95} for sFlt1/PlGF ratio, p = 0.74).ConclusionsIn women with suspected preeclampsia presenting prior to 34 weeks of gestation, sEng performs better than standard clinical evaluation in detecting adverse maternal and fetal outcomes occurring within two weeks of presentation. Soluble endoglin was strongly correlated with sFlt1 and PlGF levels, suggesting common pathogenic pathways leading to preeclampsia.

Dataset Information

Low Soluble Syndecan-1 Precedes Preeclampsia.

Introduction

Methods

Results

Conclusion

Publications

Low Soluble Syndecan-1 Precedes Preeclampsia.

Similar Datasets

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