Table 2.
Constituents of the endothelial glycocalyx and their functions.
| Glycocalyx constituents | Properties and Functions | |
|---|---|---|
| PROTEOGLYCAN: | Syndecan-1 | • Transmembrane proteoglycan containing heparan sulphate and chondroitin sulphate GAG chains • Binds chemokines and prevents them from interacting with their receptors • Serves as a cofactor for antithrombin • Release of heparan sulphate chains promotes inflammation |
| Glypican-1 | • Glycosylphosphatidylinositol anchored proteoglycan containing solely heparan sulphate GAG chains • Regulates endothelial cell inflammation, proliferation and endothelial cell-to-mesenchymal transition • Regulates arterial stiffness • Loss of glypican-1 is associated with decreased NO synthesis |
|
| GAG | Hyaluronan | • Preserves vascular integrity and homeostasis • Serves as a scaffold and microdomain for the binding and clustering of different receptors • Increased HA expression is associated with proteinuria • HA shedding and cleavage promotes inflammation |
| GLYCOPROTEINS: | Selectins | • E-selectin and P-selectin bind leukocytes through their glycosylated ligand and mediates their capture, resulting in their tethering and rolling on endothelial cells • Increased expression in inflammatory conditions • Increased in the glomerulus and interstitial microvasculature in lupus-prone mice |
| VCAM-1 | • Regulates tethering and firm adhesion of leukocytes and lymphocytes by binding to α4β1 integrin (VLA-4) and β2 integrin on immune cells • Weakly expressed in glomerular endothelial cells and proximal tubular epithelial cells in the normal kidney, increased expression in proliferative LN. • Expression is increased by cytokines, ROS, oxidized LDL • Release of VCAM-1 is associated with endothelial cell activation • VCAM-1 preserves its function in soluble form |
|
| ICAM-1 | • Regulates rolling, adhesion and crawling of leukocytes through its interaction with β2 integrin on leukocytes • Contributes to LN progression |
|
| PECAM-1 | • Regulates leukocyte extravasation | |
| Integrins | • Regulates endothelial cell and extracellular matrix interaction • Contribute to adhesion of leukocytes and platelets to the endothelium |
|
| Thrombomodulin | • Possesses anticoagulant and anti-inflammatory properties • Inhibits blood coagulation • Binds thrombin and activates Protein C |
|
| PLASMA PROTEINS: | Albumin | • Binds to proteoglycans and contributes to the structural integrity and thickness of the glycocalyx • Transports sphingosine-1-phosphate, which when bound to its receptor, inhibits MMP activation and secretion, and prevents degradation of proteoglycans |
| Antithrombin | • Binds to heparan sulphate and acts as a thrombin inhibitor | |
GAG, glycosaminoglycan; ICAM-1, intracellular cell adhesion molecule-1; MMP, matrix metalloproteinase; PECAM-1, platelet endothelial cell adhesion molecule-1; VCAM-1, vascular cell adhesion molecule-1.