The endothelial glycocalyx: a mechano-sensor and -transducer

The apical surface of endothelial cells (ECs) is decorated with various membrane-bound macromolecules that constitute the glycocalyx (GCX). As the most apical structure on the EC, the GCX senses the force (shear stress) of flowing blood and transmits the force through the cytoskeleton to sites where transduction of force to biochemical response (mechanotransduction) may occur. In this presentation, we review the structure of the GCX and experiments that demonstrate its role in mechanotransduction and vascular remodeling. Experiments with enzymes that degrade specific glycosaminoglycan components showed that the GCX mediates the shear-induced production of nitric oxide, a central process in cardiovascular control, whereas the same enzyme treatments do not affect shear-induced production of prostacyclin, another hallmark of EC mechanotransduction. These experiments reinforce the concept of distributed sites of mechanotransduction in EC. The characteristic remodeling of the EC cytoskeleton and intercellular junctions in response to shear stress are dependent on the GCX as well, and we present the experiments and theories that support the role of the GCX in these processes. The GCX is a fascinating structure whose role in EC function is only beginning to be appreciated.