keratan-sulfate and Pre-Eclampsia

Preeclampsia, an important cause of maternal and fetal morbidity and mortality, is associated with increased sFLT1 levels and with structural and functional damage to the glycocalyx contributing to endothelial dysfunction. We investigated glycocalyx components in relation to preeclampsia in human samples. While soluble syndecan-1 and heparan sulphate were similar in plasma of preeclamptic and normotensive pregnant women, dermatan sulphate was increased and keratan sulphate decreased in preeclamptic women. Dermatan sulphate was correlated with soluble syndecan-1, and inversely correlated with blood pressure and activated partial thromboplastin time. To determine if syndecan-1 was a prerequisite for the sFlt1 induced increase in blood pressure in mice we studied the effect of sFlt1 on blood pressure and vascular contractile responses in syndecan-1 deficient and wild type male mice. The classical sFlt1 induced rise in blood pressure was absent in syndecan-1 deficient mice indicating that syndecan-1 is a prerequisite for sFlt1 induced increase in blood pressure central to preeclampsia. The results show that an interplay between syndecan-1 and dermatan sulphate contributes to sFlt1 induced blood pressure elevation in pre-eclampsia.

Topics: Adult; Animals; Blood Pressure; Dermatan Sulfate; Female; Glycocalyx; Heparitin Sulfate; Humans; Keratan Sulfate; Mice; Mice, Inbred C57BL; Pre-Eclampsia; Pregnancy; Syndecan-1; Thromboplastin; Vascular Endothelial Growth Factor Receptor-1; Vasoconstriction

In this work we compared the level, localization and binding partners of a calcium binding protein, S100A6, in extracellular matrix of Wharton's jelly of healthy and preeclamptic patients.. Studies were performed on the umbilical cords taken from 10 newborns delivered by healthy and 10 newborns delivered by preeclamptic mothers. To characterize S100A6 in Wharton's jelly immunoblotting and immunohistochemistry were applied. For identification of S100A6 targets pull down assays and mass spectrometry were performed. Direct interaction of S100A6 with its targets was checked by ELISA while co-localization of these proteins was analyzed by immunofluorescence staining.. We have found that the level of S100A6 in Wharton's jelly is higher in patients with preeclampsia than in healthy ones and that post-translational modifications of S100A6 in preeclamptic tissue are different than those of S100A6 in control. We have identified several proteins that might interact with S100A6, among them are lumican and PRELP, found in Wharton's jelly of healthy and preeclamptic patients, and IGFBP-1 identified, as an S100A6 target, only in preeclamptic tissue. We have shown that the interactions between S100A6 and these proteins are direct and that IGF-1 competes with S100A6 for binding to IGFBP-1.. In Wharton's jelly of preeclamptic tissue S100A6 is up-regulated and binds to different targets than in control. This suggests involvement of S100A6 in development of preeclampsia.

Topics: Adult; Cell Cycle Proteins; Chondroitin Sulfate Proteoglycans; Extracellular Matrix; Extracellular Matrix Proteins; Female; Fluorescent Antibody Technique; Gestational Age; Glycoproteins; Humans; Immunoblotting; Immunohistochemistry; Infant, Newborn; Insulin-Like Growth Factor Binding Protein 1; Insulin-Like Growth Factor I; Keratan Sulfate; Lumican; Pre-Eclampsia; Pregnancy; Protein Processing, Post-Translational; S100 Calcium Binding Protein A6; S100 Proteins; Wharton Jelly

Pre-eclampsia--edema, proteinuria, hypertension (EPH-gestosis) is one of the more common complications observed during pregnancy. The umbilical cord vein walls were taken from newborns delivered by healthy mothers (control material) and by mothers with polysymptomatic pre-eclampsia (investigated material). Normal saphenous vein walls were collected from adult subjects undergoing varicose vein surgery. The collagen content was measured by the assay of hydroxyproline. Elastin was determined according to Fastin Elastin Assay and gravimetrically. Glycosaminoglycans content was determined by uronic acids assay. The collagen content decreased in the pre-eclampsia material. The amount of soluble elastin increased in the investigated material. The insoluble elastin content decreased in the umbilical cord veins of newborns delivered by mothers with pre-eclampsia. Reconstructing the umbilical cord vein wall may disturb fetal blood flow and affect the vascular system in adulthood.

Topics: Chondroitin Sulfates; Dermatan Sulfate; Elastin; Extracellular Matrix; Female; Glycosaminoglycans; Heparin; Humans; Hyaluronic Acid; Hydroxyproline; Infant, Newborn; Keratan Sulfate; Pre-Eclampsia; Pregnancy; Umbilical Veins

Oedema, proteinuria, hypertension (EPH)-gestosis (pre-eclampsia) is associated with a premature replacement of hyaluronic acid by sulphated glycosaminoglycans (GAGs), both in the umbilical cord arteries and in Wharton's jelly. It may be concluded from our previous report that such a phenomenon may be the result of reduction in degradation of these compounds. In order to support such a conclusion the activities of GAG-degrading enzymes in normal umbilical cord arteries and those taken from newborns delivered by mothers with EPH-gestosis were compared. It was found that EPH-gestosis results in a significant reduction in the activities of neutral endoglycosidases degrading most of the sulphated GAGs (except keratan sulphate). In the case of acidic endoglycosidases, no characteristic alterations have been found. Only the activity of heparan sulphate-degrading endoglycosidase significantly decreased. In contrast to the above-mentioned endoglycosidases, the activities of arylsulphatase B and 6-sulphatase distinctly increased. The decrease in the activities of endoglycosidases are thought to be responsible for EPH-gestosis-associated accumulation of sulphated GAGs in extracellular matrix of Wharton's jelly. This leads to the suspicion that EPH-gestosis-induced changes in the GAGs composition may alter the fibrillogenesis conditions in Wharton's jelly. The sulphated GAGs accumulated in Wharton's jelly may interact with some growth factors which modify the myofibroblasts' proliferation, gene expression, protein biosynthesis and other processes. A significance of EPH-gestosis-induced alteration in Wharton's jelly is discussed.

Topics: beta-Galactosidase; beta-N-Acetylhexosaminidases; Chondroitin Sulfates; Dermatan Sulfate; Female; Glycosaminoglycans; Glycoside Hydrolases; Heparin; Heparitin Sulfate; Humans; Hydrogen-Ion Concentration; Infant, Newborn; Keratan Sulfate; Pre-Eclampsia; Pregnancy; Sulfatases; Umbilical Cord