A sticky proposition: The endothelial glycocalyx and von Willebrand factor

Abstract

Von Willebrand factor (VWF) is a critical component of the hemostatic system. Basal secretion of VWF from endothelial cells is the principal determinant of an individual's baseline plasma VWF levels, while endothelial VWF release can also be induced by several biochemical agonists and biomechanical forces such as increased shear stress. However, the mechanotransduction machinery responsible for this latter response is unclear. Here we propose that the endothelial glycocalyx (EGC), a dynamic layer of proteins and carbohydrates that covers the surface of the vascular endothelium, may play a key role in mediating this response. The EGC has previously been implicated in mediating the mechanotransduction of shear stress in other shear‐responsive endothelial processes, such as nitric oxide production and stem cell differentiation. Here, we hypothesize that a similar mechanism may be responsible for the basal secretion of endothelial VWF, whereby the EGC mediates the mechanotransduction of physiological shear stress generated by flowing blood, that in turn contributes to the maintenance of physiological plasma VWF levels.

The Role of the Glycocalyx in the Pathophysiology of Subarachnoid Hemorrhage-Induced Delayed Cerebral Ischemia

“…Adhesion molecules, e.g., vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1), act as endothelial ligands for integrins and play a crucial role in leukocyte adhesion to the endothelium. In healthy vasculature, the glycocalyx components (thickness range: 400 -500 nm) cover these cell-adhesion molecules (thickness range: 20 -40 nm) on the endothelium, thereby preventing them from interacting with their ligands (Reitsma et al, 2007;Lipowsky, 2012;Choi and Lillicrap, 2020). Hence, an intact glycocalyx isolates the endothelium from circulating inflammatory cells, and limits inflammatory processes (Figure 1).…”

“…This leads to the production of endothelial prostacyclins that prevent platelets and neutrophils from binding to the endothelium (Iba, 2016). The glycocalyx also forms an anchorage point for the von Willebrand factor (vWF) (Choi and Lillicrap, 2020). In the presence of non-physiological or increased shear stress, the vWF changes its configuration and extends into the lumen to bind platelets.…”

COVID-19 and Delayed Cerebral Ischemia—More in Common Than First Meets the Eye

“…The net negative charge of the glycocalyx, generated by the anionic oligosaccharides from which it is composed, results in an electrostatic repulsion against platelets and red blood cells, whilst the depth of the glycocalyx helps to physically separate blood cells from the endothelial surface. To date, there is limited literature available on the interaction between vWF and the glycocalyx; however, some studies suggest that the glycocalyx plays a role in tethering secreted and circulating vWF to the endothelium [ 7 , 8 ].…”

Circulating Syndecan-1 and Tissue Factor Pathway Inhibitor, Biomarkers of Endothelial Dysfunction, Predict Mortality in Burn Patients

“…The endothelial glycocalyx layer (EGL) is a complex network of proteoglycans and glycoproteins on the luminal surface of blood vessels that maintains vessel integrity and regulates inflammation, blood clotting, and flow ( 7 , 8 ). Proteolytic release of EGL components (shedding) occurs in response to a number of physiologic challenges and results in detrimental systemic effects ( 9 ).…”