Heparan sulfate proteoglycan (HSPG) and heparin (HSPG)

Heparan sulfate proteoglycans (HSPGs) are a class of complex glycoproteins found on the cell surface and within the extracellular matrix, consisting of a core protein covalently linked to heparan sulfate glycosaminoglycan chains (Sarrazin et al., 2011, Cold Spring Harb Perspect Biol). They play a fundamental role in biological processes by acting as co-receptors for a wide array of ligands, including fibroblast growth factors (FGFs), vascular endothelial growth factors (VEGFs), and various chemokines, thereby facilitating signal transduction and regulating cell proliferation and migration (Bishop et al., 2007, Nature). Heparin, a highly sulfated form of heparan sulfate primarily produced by mast cells, is a potent anticoagulant that functions by binding to and activating antithrombin III, which subsequently inactivates thrombin and Factor Xa (Gallagher, 2015, J Clin Invest). In pathological contexts, HSPGs are involved in tumor angiogenesis and metastasis, as well as serving as attachment sites for numerous viruses, including SARS-CoV-2 and Herpes Simplex Virus (Varki et al., 2015, Essentials of Glycobiology). Therapeutic interventions targeting this system include the administration of exogenous heparin or low-molecular-weight heparins for thrombosis, and the development of heparin mimetics designed to disrupt growth factor signaling or inhibit heparanase in cancer (Knelson et al., 2014, Nat Rev Cancer).

Other names

Heparan sulfateHeparinHS-GAGHeparan sulfate glycosaminoglycanCell surface proteoglycanSyndecanGlypicanPerlecanAgrin

Potentiation of antithrombin III to inhibit thrombin and Factor Xa; competitive inhibition of growth factor binding to cell surface receptors; inhibition of heparanase enzyme activity; blockade of viral attachment to host cells; neutralization of heparin activity by basic proteins like protamine.