Physiological, Pathophysiological and Therapeutic Roles of Heparin and Heparan Sulfate

Heparin and heparan sulfate belong to the glycosaminoglycan (GAG) family of carbohydrates. They are linear acidic complex polysaccharides found on the cell surface and in the extracellular matrix. Heparin and heparan sulfate GAGs are biosynthesized as proteoglycans (PGs) with multiple GAG chains linked to a variety of core proteins. Heparin PGs are found exclusively in the granules of subsets of mast cells, whereas heparan sulfate PGs have a much greater distribution in the body, being associated with stromal matrices, basement membranes, and almost all cell surfaces. Heparin and heparan sulfate PGs interact with cell surface binding proteins and are internalized by receptor-mediated endocytosis through their GAG chains. Heparin and heparan sulfate are the most intensively studied GAGs as a result of their anticoagulant properties. However, it has become obvious that heparin and heparan sulfate not only have anticoagulant activities but also exhibit a number of diverse biological functions including ones regulating cell growth and differentiation, inflammatory processes, host defense and viral infection mechanisms, cell–cell and cell–matrix interactions, lipid transport, and clearance/metabolism. These functions result from the direct interactions between heparin and heparan sulfate and heparin-binding proteins.