Low Soluble Syndecan-1 Precedes Preeclampsia.
BACKGROUND
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.


CONCLUSIONS
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.
Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.|Department of Obstetrics, Gynecology & Reproductive Sciences, Division of Maternal Fetal Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
Robin E
RE
Gandley
Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
Andrew
A
Althouse
Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.|Department of Obstetrics, Gynecology & Reproductive Sciences, Division of Maternal Fetal Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.|Clinical and Translational Research Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
Arundhathi
A
Jeyabalan
Department of Obstetrics, Gynecology & Reproductive Sciences, Division of Maternal Fetal Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
Julia M
JM
Bregand-White
Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
Stacy
S
McGonigal
Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
Ashley C
AC
Myerski
Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
Marcia
M
Gallaher
Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.|Department of Obstetrics, Gynecology & Reproductive Sciences, Division of Maternal Fetal Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
Robert W
RW
Powers
Department of Obstetrics, Gynecology & Reproductive Sciences, Division of Maternal Fetal Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
Carl A
CA
Hubel
D000293:Adolescent; D000328:Adult; D001724:Birth Weight; D016022:Case-Control Studies; D005260:Female; D015870:Gene Expression; D006801:Humans; D007231:Infant, Newborn; D010920:Placenta / Q000378:metabolism / Q000473:pathology*; D011225:Pre-Eclampsia / Q000097:blood* / Q000175:diagnosis / Q000235:genetics / Q000473:pathology*; D011247:Pregnancy; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D053668:Syndecan-1 / Q000032:analysis / Q000097:blood* / Q000235:genetics; D014327:Trophoblasts / Q000378:metabolism / Q000473:pathology; D055815:Young Adult
D012333:RNA, Messenger; D053668:Syndecan-1