Placental Syncytiotrophoblast Maintains a Specific Type of Glycocalyx at the Fetomaternal Border: The Glycocalyx at the Fetomaternal Interface in Healthy Women and Patients With HELLP Syndrome

Hofmann-Kiefer, Klaus; Chappell, Daniel; Knabl, Julia; Frank, Hans-Georg; Martinoff, Nadja; Conzen, P.; Becker, Bernhard F.; Rehm, Markus

doi:10.1177/1933719113483011

Cited by 19 publications

(9 citation statements)

References 43 publications

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“…Hoffman-Kiefer et al demonstrated that HS chain fragments, a major component of the placental glycocalyx, were increased in the circulation of women with HELLP syndrome (Hemolysis, Elevated Liver enzymes, and Low Platelet count), often considered an acute stage and extremely severe relative of preeclampsia [19,20]. Additional studies have demonstrated the importance of the HS chains in normal pregnancy to regulate sFLT-1 localization in the placenta [11].…”

Section: Discussionmentioning

confidence: 99%

Heparanase regulation of sFLT-1 release in trophoblasts in vitro

2019

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Introduction: Preeclampsia is a common pregnancy disorder which is characterized by new onset hypertension and endothelial dysfunction. Despite efforts to determine the causal factors of this disease, little progress has been made in discerning the etiology. The hypoxic and ischemic placenta, however, is generally accepted as the source for secreted factors in the maternal circulation, such as sFLT-1, which drive the maternal syndrome. Methods: Using BeWo placental trophoblast cells, we measured the role of hypoxia on sFLT-1 mRNA as well as protein production. We also exposed the cells to treatment with heparin and heparanase inhibitor OGT-2115. Results: We found that under hypoxic conditions mRNA levels of sFLT-1 were unchanged compared to normoxic controls. Although the message level did not differ under hypoxic conditions, the sFLT-1 release into the media was significantly greater in hypoxia. Additionally, we found that sFLT-1 is able to bind heparan strands in the extracellular matrix with its heparin binding site. These heparan strands can be cleaved by the extracellular enzyme heparanase. We found that heparanase expression was significantly increased in hypoxia, and inhibiting the actions of heparanase attenuated the release of sFLT-1 into the media. Discussion: While the placenta remains a source of sFLT-1, the mechanism of increased circulating sFLT-1 may differ than simple upregulation of the protein. These data demonstrate the potential importance of the role heparanase may play in releasing previously made sFLT-1 into the maternal circulation.

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Section: Discussionmentioning

confidence: 99%

Heparanase regulation of sFLT-1 release in trophoblasts in vitro

2019

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“…There is also evidence of an elevated level of HA in the blood in the PE [64, 65] and HELLP syndromes [66]. The level of antibodies to HA and its structural disaccharide are also elevated in PE [67, 68].…”

Section: Regulatory Effect Of Ha Polymers Of Various Sizesmentioning

confidence: 99%

Hyaluronic Acid in Vascular and Immune Homeostasis during Normal Pregnancy and Preeclampsia

et al. 2016

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Preeclampsia (PE) is a multisystem pathologic state that clinically manifests itself after the 20th week of pregnancy. It is characterized by high maternal and perinatal morbidity and mortality. According to modern concepts, the impairment of trophoblast invasion into maternal spiral arteries, leading to the development of ischemia in placenta, is considered to be the major pathogenetic factor of PE development. Ischemic lesions initiate the development of a systemic inflammatory response (SIR) and endothelial dysfunction, which is the main cause of the multiple organ failure in PE. Some data has appear indicating the importance of a glycans-forming endothelial glycocalyx and extracellular matrix (ECM) for placenta morphogenesis, as well as their role in the regulation of vascular permeability and vascular tone in hypertension disorders and, in particular, PE. Since intact glycocalyx and ECM are considered to be the major factors that maintain the physiological vascular tone and adequate intercellular interactions, their value in PE pathogenesis is underestimated. This review is focused on hyaluronic acid (HA) as the key glycan providing the organization and stabilization of the ECM and glycocalyx, its distribution in tissues in the case of presence or absence of placental pathology, as well as on the regulatory function of hyaluronic acids of various molecular weights in different physiological and pathophysiological processes. The summarized data will provide a better understanding of the PE pathogenesis, with the main focus on glycopathology.

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“…The surface of eukaryotic cells has a hydrated matrix of specialized proteoglycans and glycoproteins, linked to the plasma membrane, known as the glycocalyx [ 3 , 4 ] The vascular endothelial glycocalyx is a critical regulator of vascular function, and endothelial glycocalyx damage has been implicated in reperfusion oxidative injury, inflammation, atherosclerosis and diabetes [ 3 , 5 – 10 ]. The syncytiotrophoblast microvillous membrane surface also has a substantial glycocalyx [ 11 – 13 ] but its functions are poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Low Soluble Syndecan-1 Precedes Preeclampsia

et al. 2016

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IntroductionSyndecan-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.MethodsWe 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.ResultsIn 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.ConclusionSoluble 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.

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Placental Syncytiotrophoblast Maintains a Specific Type of Glycocalyx at the Fetomaternal Border: The Glycocalyx at the Fetomaternal Interface in Healthy Women and Patients With HELLP Syndrome

Cited by 19 publications

References 43 publications

Heparanase regulation of sFLT-1 release in trophoblasts in vitro

Heparanase regulation of sFLT-1 release in trophoblasts in vitro

Hyaluronic Acid in Vascular and Immune Homeostasis during Normal Pregnancy and Preeclampsia

Low Soluble Syndecan-1 Precedes Preeclampsia

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