Endothelial glycocalyx as a critical signalling platform integrating the extracellular haemodynamic forces and chemical signalling

Abstract

The glycocalyx covers the human mammalian cells and plays important roles in stroke, inflammation and atherosclerosis. It has also been shown to be involved in endothelial mechanotransduction of shear stress. Shear stress induces the remodelling of the major component of the glycocalyx including glypican-1, a cell membrane heparan sulphate proteoglycan. Other factors, such as sphingosine-1-phosphate (S1P), protect the glycocalyx against syndecan-1 ectodomain shedding and induce the synthesis of heparan sulphate. In this study, we reviewed the role of shear stress and S1P in glycocalyx remodelling and revealed that the glycocalyx is a critical signalling platform, integrating the extracellular haemodynamic forces and chemical signalling, such as S1P, for determining the fate of endothelial cells and vascular diseases. This review integrated our current understanding of the structure and function of the glycocalyx and provided new insight into the role of the glycocalyx that might be helpful for investigating the underlying biological mechanisms in certain human diseases, such as atherosclerosis.

Keywords: glycocalyx; shear stress; sphingosine-1-phosphate.

Figure 1

Structure of the endothelial glycocalyx. The endothelial glycocalyx is located at the luminal side of vascular endothelial cells and its soluble components are directly in contact with the bloodstream. The endothelial glycocalyx is mainly composed of glycoproteins bearing acidic oligosaccharides and terminal sialic acids (SA), proteoglycans (PG), such as heparan sulphate proteoglycans (HSPGs; syndecan family and glypican‐1), and glycosaminoglycan (GAG) side chains. The predominant GAGs in endothelial cells are heparan sulphate (HS), chondroitin sulphate (CS) and hyaluronic acid (hyaluronan, HA). HS and CS are attached to PGs. HA binds with receptor CD44. Syndecans (including syndecan‐1, syndecan‐2, syndecan‐3 and syndecan‐4) are single transmembrane domain proteins. Glypican‐1 is an extracellular glycosylphosphatidylinositol (GPI)‐anchored protein, which is localized in lipid rafts. Syndecan‐1 and CD44 interact with the cytoskeleton.

Figure 2

The glycocalyx acts as a signalling platform. Different signalling pathways involved in cellular function, in conditions with or without the glycocalyx. The glycocalyx acts as a signalling platform. Once the platform is destructed, the interplay among these factors and the underlying signalling pathways might be changed.