Glycocalyx and its involvement in clinical pathophysiologies

Abstract

Vascular hyperpermeability is a frequent intractable feature involved in a wide range of diseases in the intensive care unit. The glycocalyx (GCX) seemingly plays a key role to control vascular permeability. The GCX has attracted the attention of clinicians working on vascular permeability involving angiopathies, and several clinical approaches to examine the involvement of the GCX have been attempted. The GCX is a major constituent of the endothelial surface layer (ESL), which covers most of the surface of the endothelial cells and reduces the access of cellular and macromolecular components of the blood to the surface of the endothelium. It has become evident that this structure is not just a barrier for vascular permeability but contributes to various functions including signal sensing and transmission to the endothelium. Because GCX is a highly fragile and unstable layer, the image had been only obtained by conventional transmission electron microscopy. Recently, advanced microscopy techniques have enabled direct visualization of the GCX in vivo, most of which use fluorescent-labeled lectins that bind to specific disaccharide moieties of glycosaminoglycan (GAG) chains. Fluorescent-labeled solutes also enabled to demonstrate vascular leakage under the in vivo microscope. Thus, functional analysis of GCX is advancing. A biomarker of GCX degradation has been clinically applied as a marker of vascular damage caused by surgery. Fragments of the GCX, such as syndecan-1 and/or hyaluronan (HA), have been examined, and their validity is now being examined. It is expected that GCX fragments can be a reliable diagnostic or prognostic indicator in various pathological conditions. Since GCX degradation is strongly correlated with disease progression, pharmacological intervention to prevent GCX degradation has been widely considered. HA and other GAGs are candidates to repair GCX; further studies are needed to establish pharmacological intervention. Recent advancement of GCX research has demonstrated that vascular permeability is not regulated by simple Starling’s law. Biological regulation of vascular permeability by GCX opens the way to develop medical intervention to control vascular permeability in critical care patients.

Increased Serum Hyaluronic Acid and Heparan Sulfate in Dengue Fever: Association with Plasma Leakage and Disease Severity

“…Further studies involving both children and adults with prospective profiling of glycocalyx components are needed to delineate their roles in dengue pathogenesis and potential as prognostic markers. In addition, interventions to attenuate damage or reconstitute the glycocalyx may have therapeutic potential to decrease vascular leakage in dengue32.…”

Association of impaired endothelial glycocalyx with arterial stiffness, coronary microcirculatory dysfunction, and abnormal myocardial deformation in untreated hypertensives

“…To be more specific, transmission of shear stress forces to endothelial cells, which are induced by blood flow, causes changes in the structure and architecture of glycocalyx, triggers the release of nitric oxide, and as a result contributes to the regulation of vasomotor tone. Hence, glycocalyx participates, through this rheological mechanism, in the maintenance of homeostasis of the peripheral tissues . Indeed, denudation of the glycocalyx by heparinase III reduced NO production, hence the glycocalyx is deemed to play a significant role in the regulation of vasomotor tone .…”

“…30 In agreement with these studies, in our study, we have shown that there is an association between impaired glycocalyx, as assessed by Hence, glycocalyx participates, through this rheological mechanism, in the maintenance of homeostasis of the peripheral tissues. 31,32 Indeed, denudation of the glycocalyx by heparinase III reduced NO production, hence the glycocalyx is deemed to play a significant role in the regulation of vasomotor tone. 33 To this end in our study, we have found a close association between reduced endothelial glycocalyx thickness and impaired coronary flow reserve, which is at least partly NO dependent.…”

Increase in perfused boundary region of endothelial glycocalyx is associated with higher prevalence of ischemic heart disease and lesions of microcirculation and vascular wall

“…Endothelial glycocalyx covers the monolayer and plays important role in maintenance of endothelial integrity . Endothelial glycocalyx regulates endothelial barrier, shear stress, and microenvironment of endothelial monolayer as well as its interaction with various blood cells …”