Glycoconjugates of bood vessels endothelium

An extracellular coating was discovered by Bennet in 1963 on the luminal surface of endothelia and termed “glycocalyx”. Apparent thickness of the glycocalyx is ~ 0,5 μm. The glycocalyx consists of: proteoglycans, glycosaminoglycans (GAGs) and oligosaccharide chains of glycoproteins (some containing sialic acid residues). The amount of glycocalyx sulfate proteoglycan (SPG)-molecules vary between 105 –106 / cell. SPG are composed of: heparan sulfate (HS), chondroitin sulfate (CS), dermatan sulfate (DS), and keratan sulfate (KS) attached to a core protein by GlcAGal-Gal-Xyl-Ser. Biosynthesis of GAGs occurs mainly in Golgi, with exception of HA which is synthesized at the cell membrane. Fine structure of GAGs is tissue and cell type specific, dependent on aging and pathology. All GAGs form unbranched chains 30–150 disaccharide units, with exception of hyaluronic acid (HA) forming much longer chains. The GAGs hexosamines may be sulfated at 4 or 6-position. CS is the most abundant GAG in the body. HS has a few sulfate rich oligosaccharide units, separated by longer sulfate free or poor sequences. KS is heterogenic. HA is not connected with protein by covalent bond. More than 100 different proteins interact with HS. One type of HS-protein binding depends on relatively rare modifications, and the second on the arrangement of relatively common disaccharides. The vascular endothelium GAGs are attached mostly to syndecanstransmembrane proteoglycans and glypicans anchored to the cell membrane by glycosylphosphatidylinoinositol (GPI) linkage. Syndecans, which may be receptors or co-receptors for: growth factors, enzymes (lipoprotein lipase), viruses, proteases and protease inhibitors, are 22–46 kDa core proteins carrying 3–4 HS chains located distally, and 0–4 CS proximally at ectodomain, with cytosolic domains involved in intracellular signaling.. Syndecans are shed from the cell surface by TIMP-3-sensitive MMP cleavage of the core protein, located in immediate proximity to the transmembrane domain. Glypicans (59–65 kDa proteins carrying 2–5 HS chains) are involved in the suppression/modulation of growth and the activity of growth factors. L15.2