**5.2. Alteration of endothelial glycocalyx in preeclampsia**

The signs of endothelial activation are the expression of activation markers by endothelial cells and increased plasma concentrations of the soluble forms of CAMs and of the factors, regulating angiogenesis and blood clotting. However, the main feature of the evolving endothelial activation is alteration, damage and shedding of the eGC and an increase of its components concentration in blood. Currently, there are limited studies of this phenomena in PE, but available reports show significant alteration of eGC composition in the placental structures in PE [164]. The most prominent alteration of the eGC composition was found in the placentas of women with severe PE. Alterations take place also in the eGC capillaries of terminal placental villi: the content of glycans with terminal β-galactosyl and α-mannosyl residues increase, while the content of α2,3-linked sialic acids decrease in the glycome in severe PE [165]. These alterations are supposed to point to the exposure of glycans bearing the "danger signals" and being the counter-receptors for endogenous lectins; interaction with these activate maternal immune system [166, 167] (REF). Such studies, performed by immunohistochemistry of placenta after childbirth and using the lectins panel or monoclonal antibodies to carbohydrates antigens, give an idea of alterations of the placental glycome and its separate structures, including capillary endothelium, and provide evidence obtained by direct eGC visualization [165, 168]. Since direct visualization of the eGC is impossible in clinical trials where no surgical tissue sampling is implied, in these cases, an indirect assessment of the content of the degradation products of eGC is used.

Indirect methods have significant limitations, but they are the only possibility to evaluate the eGC *in vivo*. Indirect assessment of the eGC by ELISA show that in PE, the plasma content of the structural proteoglycans (endocan-1, syndecan-1, decorin and HA) and the GAGs of eGC increase [169–171]. Serum endocan concentrations were significantly elevated in women with PE versus normotensive controls, and concentrations seem to be associated with the severity of the disease [172]. 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 obstetrical syndromes and uncomplicated pregnancies [173]. It is suggested that in PE, the maternal endothelium is a source of GAGs in blood, and intensive eGC shedding thus indicates a manifestation of endothelial dysfunction [169–174]. Also, patients with PE show GAGs excretion in urine; this is thought to be linked with the eGC proteoglycans alterations and with the glomerular basement membrane changes, and associated with proteinuria [175]. *In vitro* and *in vivo* experimental studies, using cell and animal models is another opportunity of indirect eGC evaluation. This approach was used to study CKD [74, 75], cardio-vascular and inflammatory diseases [13, 176], cancer [13, 176, 177]—the conditions manifestating with hypertension, proteinuria, edema, SIR, thrombosis. The results of such studies provide some keys to PE, which is less studied, but exhibits similar clinical signs. Experimental models allow to evaluate not only the degree of the eGC damage by various factors (SIR being the most significant), but also the molecular changes of the eGC composition. This moment is a crucial point because SIR is not a specific process; it accompanies almost any pathology and promotes the generation of neoantigens, acting as an adaptive response trigger and provoking autoimmune reactions.
