Endothelial Glycocalyx: Permeability Barrier and Mechanosensor

Abstract

Endothelial cells are covered with a polysaccharide rich layer more than 400 nm thick whose mechanical properties limit access of circulating plasma components to endothelial cell membranes. The barrier properties of this endothelial surface layer are deduced from the rate of tracer penetration into the layer and the mechanics of red and white cell movement through capillary microvessels. This review compares the mechanosensor and permeability properties of an inner layer (100–150 nm, close to the endothelial membrane) characterized as a quasi-periodic structure which accounts for key aspects of transvascular exchange and vascular permeability with those of the whole endothelial surface layers. We conclude that many of the barrier properties of the whole surface layer are not representative of the primary fiber matrix forming the molecular filter determining transvascular exchange. The differences between the properties of the whole layer and the inner glycocalyx structures likely reflect dynamic aspects of the endothelial surface layer including tracer binding to specific components, synthesis and degradation of key components, activation of signaling pathways in the endothelial cells when components of the surface layer are lost or degraded, and the spatial distribution of adhesion proteins in microdomains of the endothelial cell membrane.

Syndecan-1 in Acute Decompensated Heart Failure – Association With Renal Function and Mortality –

“…Glycocalyx also modulates the inflammatory response by preventing leukocyte adhesion and by binding numerous ligands, including chemokines, cytokines and growth factors. 13, 14 Many of the functions of glycocalyx are related to the pathophysiologic processes involved in the development of AKI and can also contribute to increased morbidity and mortality. 15 Syndecan-1 is a biomarker of endothelial glycocalyx damage and it has been shown to be increased in patients suffering acute myocardial infarction.…”

Plasma syndecan-1 and heparan sulfate correlate with microvascular glycocalyx degradation in hemorrhaged rats after different resuscitation fluids

“…The endothelial glycocalyx, an integral component of the endothelial barrier, is composed of membrane-spanning backbone molecules of proteoglycans (syndecans and glypican-1), with associated side-chain molecules made of glycosaminoglycans (heparan sulfate, chondroitin sulfate, and hyaluronan), and glycoproteins that are membrane-bound (12,19,65). The endothelial glycocalyx plays an essential role in many physiological functions such as lipid homeostasis regulation, permeability, inflammation, coagulation, and mechanotransduction of shear stress, leading to changes in local blood flow (19,41,43).…”

The Circulating Glycosaminoglycan Signature of Respiratory Failure in Critically Ill Adults

“…In vivo, the glycocalyx forms a thick endothelial surface layer (ESL) that contributes to the regulation of endothelial permeability, leukocyte adhesion, and nitric oxide production (2)(3)(4). Accordingly, degradation of the ESL has been implicated in the pathogenesis of critical illnesses (e.g.…”