Table 2.

Clinical and experiment research of glycocalyx and/or its components in pre-eclampsia.

№	Study Subject	Methods	Measurement	Findings
1	Sweden, 42 patients (11 with PE and eclampsia)	Case–control study ELISA	Plasma HA levels	Plasma HA level is increased in severe PE and eclampsia [46].
2	South Africa, 84 patients (28 with PE)	Dimethyl-methylene blue assay	Urinary HSPGs and CSPGs levels	Urinary excretion of HSPGs was significantly increased in the PE group compared to the normotensive pregnant group and the hypertensive nonproteinuric group [44]
3	Italy, 118 patients (93 with hypertensive disorders in pregnancy, 32 with PE)	Case–control study Lectin histochemistry	Intensity of staining of carbon residues in the glycans with lectins in the placental tissue	Various alterations of the carbohydrate metabolism and GC compositions in the placentas from women with hypertensive disorders indicate correlation with the placental morpho-functional changes, characteristic for these complications, and with the degree of clinical severity [47].
4	Germany, 55 patients (17 with HELLP-syndrome)	Observational study ELISA	GC components (sdc1, HS, and HA) were measured in serum	Increased serum levels of HS and HA were only detected in patients with HELLP. Considerable amounts of sdc1 are released into maternal blood during uncomplicated pregnancy. The HELLP syndrome is associated with an even more pronounced shedding of GC components. Maternal vasculature as well as placenta may be a possible origin of circulating GC components [48].
5	Germany, 16 patients (8 with HELLP-syndrome)	Case–control study Immunohistochemistry Electron microscopy	Visualization and expression assessment of GC components (sdc1, HS, HA) in placenta	Large amounts of sdc1 were found, but neither HA nor HS as the major components. Intravillous fetal endothelium did not express any of the investigated GAGs. Healthy women and patients with HELLP showed no differences concerning GC composition and thickness of the syncytiotrophoblast [49].
6	UK, 75 patients (17 with PE)	ELISA Glycosaminoglycan assay Immunohistochemistry	Concentration and expression sdc1 and sulfated GSGs in placental tissues	Decreased sGAGs and sdc1 in PE were not related to labor, gestational age, and birthweight centile [50].
7	Brazil, 153 patients (60 with PE)	ELISA	Serum HA levels	Increased release of HA may contribute to an elevated pro-inflammatory response and tissue damage in women with PE [51].
8	Turkey, 81 patients (49 with PE)	A cross-sectional study ELISA	Serum endocan levels	Mean endocan levels were not significantly different among groups [42].
9	China, 22 patients (12 with PE)	Case–control study Immunohistochemistry; qRT-PCR; Western blotting; ELISA	Immunohistochemistry was used to evaluate the location of endocan. Then, the mRNA and protein levels of endocan in placenta were detected using qRT-PCR and Western blotting. Serum endocan concentration was measured by ELISA	Expression of endocan mRNA and protein were increased in the placenta tissues of PE compared with in the normal pregnancy; however, the endocan concentration of maternal serum did not differ significantly [43,52].
10	Brazil, 117 patients (50 with PE)	Observational and case–control study MagPlex(TH)-C	Plasma endocan-1 levels	Endocan-1 is increased in women with PE. The negative correlations between endocan-1 and clinical data suggest that this molecule may also be involved in prematurity and low birth weight [53].
11	USA, 506 patients (130 with uncomplicated pregnancy; 102 with PE; 274 with other great obstetrical syndromes)	A cross-sectional study ELISA	Plasma endocan-1 concentrations	Median maternal plasma endocan concentrations were higher in PE patients and lower in acute pyelonephritis with bacteremia than in uncomplicated pregnancy. No significant difference was observed in the median plasma endocan concentration between other great obstetrical syndromes and uncomplicated pregnancies. The difference in changes of endocan in PE and acute pyelonephritis with bacteremia may confirm that the two diseases differ in pathogenetic mechanisms, despite their associations with systemic vascular inflammation and endothelial cell activation/dysfunction [54].
12	Russia, 23 patients (16 with moderate and severe PE)	Case–control study Lectin histochemistry	The study of carbohydrate phenotype of placenta was carried out by the lectin staining of syncytiotrophoblast membranes and the membranes of endothelial cells of terminal placental villi	The most prominent alteration of the GC composition was found in the placentas of women with severe PE. The modified glycome of syncytiotrophoblast and capillary endothelium may play an important role in pathogenesis of PE [55].
13	Canada, 28 patients (14 with PE)	Retrospective and case–control study qRT- PCR; situ hybridization; ELISA	Decorin expression was measured at tissue and cell levels in the placenta sections. Retrospective measurements of plasma decorin levels during the second trimester were carried out.	Decorin overexpression by basal decidual cells is associated with hypoinvasive phenotype and poor endovascular differentiation of trophoblast cells in PE. Elevated plasma decorin concentration is a potential predictive biomarker for PE before the onset of clinical signs [56].
14	Turkey, 129 patients (99 with PE)	A cross-sectional study ELISA	Serum endocan-1 concentrations	Serum endocan concentrations were significantly elevated in women with PE versus normotensive controls, and concentrations seemed to be associated with the severity of the disease [57].
15	Serbia, 44 patients (14 with PE + IUGR)	Case–control study DSA-FACE method; electrophoresis; lectin and immunoblotting; lectin affinity chromatography	N-glycan analysis in placenta	Glycans on placental membranes were altered due to PE [58].
16	USA, longitudinal study (n = 8); cross-sectional 3rd trimester study (34 patients, 17 with PE); case–control study (44 patients (19 with PE)	Case–control, longitudinal, and cross- sectional studies. ELISA Isolation and analysis of placental RNA Placental immunohistochemical staining and scoring	Plasma sdc1 levels and placental sdc1 expression	Soluble sdc is significantly lower before the clinical onset of PE, with reduced expression of sdc1 in the placenta after expulsion, suggesting a role of GC disturbance in PE pathophysiology [59].
17	Turkey, 80 patients (27 with EO- PE and 27 LO- PE)	Cross-sectional study ELISA	Serum sdc1 levels	Control group presented significantly higher sdc1 levels, than EO and LO-PE [52].
18	Brasil, 60 patients (20 with PE)	ELISA	Plasma HA levels	Significantly higher plasma levels of HA in PE than in normotensive pregnant women and non-pregnant women, suggesting involvement of HA as DAMPs in SIR [60].
19	USA, 137 women (14 with EO-PE, 29 with LO-PE)	ELISA and noninvasive sublingual eGC measurements by sidestream dark field imaging	Plasma levels of sdc1, HA, HSPGs, perfused boundary region (width of the eGC that was permeable to RBCsreflects eGC degradation) and the percentage of vessels that were filled with RBCs ≥50% of the time (this reflects a microvascular perfusion)	In LO-PE the structural eGC changes (eGC degradation, larger perfused boundary region) was higher and percentage of vessels that were filled with RBCs was significantly lower) were accompanied by elevated plasma concentration of eGC components [61].
20	Turkey, 78 women (25 with EO-PE and 16 with LO-PE)	ELISA	Plasma endocan levels	There was no significant difference between endocan levels in EO-PE or LO-PE compared with their corresponding control groups, nor between EO- and LO-PE groups [62].
21	Poland, 60 women (20 with EO-PE and 20 with LO-PE)	ELISA	Serum HA and sdc1 levels	Concentration of HA was significantly higher and the level of sdc1 was significantly lower in patients with EO and LO-PE than in the control group [63].
22	Austria, single center nested case–control study, 107 patients (95 with normal pregnancy, 12 with PE)	ELISA	Serum sdc1 levels were measured at 10 dynamic points during pregnancy	Sdc1 levels were lower in women developing PE compared to normal pregnancies, and sdc-1 might be useful to predict PE. After delivery, sdc1 levels remained higher in women with PE [64].