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Glycocalyx and its involvement in clinical pathophysiologies

View Article: PubMed Central - PubMed

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.

No MeSH data available.


Typical experimental methods used to analyze GCX/ESL function. a Fluorescent-labeled leukocytes in microvasculature. To quantify the leukocyte-endothelium interaction, fluorescence-labeled leukocytes in flowing blood were observed within a region of interest (ROI) during a 30-s video recording, and adhesive and/or rolling leukocytes were counted. b Permeable analysis using FITC dextran. To analyze vascular permeability, fluorescence-labeled dextran was injected and time-dependent changes in brightness within an ROI (yellow box) set over the interstitium were identified using image analysis software. (These images were originally obtained by H. Kataoka)
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Fig3: Typical experimental methods used to analyze GCX/ESL function. a Fluorescent-labeled leukocytes in microvasculature. To quantify the leukocyte-endothelium interaction, fluorescence-labeled leukocytes in flowing blood were observed within a region of interest (ROI) during a 30-s video recording, and adhesive and/or rolling leukocytes were counted. b Permeable analysis using FITC dextran. To analyze vascular permeability, fluorescence-labeled dextran was injected and time-dependent changes in brightness within an ROI (yellow box) set over the interstitium were identified using image analysis software. (These images were originally obtained by H. Kataoka)

Mentions: Although the morphological profile of the GCX has begun to be elucidated, functional analyses are now needed to clarify the roles of the GCX. Receptors on the surface of the endothelium are assumed to hinder behind the GCX, and the degradation of the GCX exposes these receptors and triggers leukocyte-endothelial interactions. Lipopolysaccharide (LPS) may be a useful tool for triggering GCX degradation [34]. GCX degradation leads exteriorization of ICAM-1 (intercellular adhesion molecule 1) and/or VCAM-1 (vascular cell adhesion molecule 1) to the lumen of vasculature, which enhances leukocyte-endothelial interactions [35, 36]. The rolling leukocyte on the vessel wall is visualized in the septic model where the leukocyte is labeled with rhodamine 6G (Fig. 3a).Fig. 3


Glycocalyx and its involvement in clinical pathophysiologies
Typical experimental methods used to analyze GCX/ESL function. a Fluorescent-labeled leukocytes in microvasculature. To quantify the leukocyte-endothelium interaction, fluorescence-labeled leukocytes in flowing blood were observed within a region of interest (ROI) during a 30-s video recording, and adhesive and/or rolling leukocytes were counted. b Permeable analysis using FITC dextran. To analyze vascular permeability, fluorescence-labeled dextran was injected and time-dependent changes in brightness within an ROI (yellow box) set over the interstitium were identified using image analysis software. (These images were originally obtained by H. Kataoka)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC5017018&req=5

Fig3: Typical experimental methods used to analyze GCX/ESL function. a Fluorescent-labeled leukocytes in microvasculature. To quantify the leukocyte-endothelium interaction, fluorescence-labeled leukocytes in flowing blood were observed within a region of interest (ROI) during a 30-s video recording, and adhesive and/or rolling leukocytes were counted. b Permeable analysis using FITC dextran. To analyze vascular permeability, fluorescence-labeled dextran was injected and time-dependent changes in brightness within an ROI (yellow box) set over the interstitium were identified using image analysis software. (These images were originally obtained by H. Kataoka)
Mentions: Although the morphological profile of the GCX has begun to be elucidated, functional analyses are now needed to clarify the roles of the GCX. Receptors on the surface of the endothelium are assumed to hinder behind the GCX, and the degradation of the GCX exposes these receptors and triggers leukocyte-endothelial interactions. Lipopolysaccharide (LPS) may be a useful tool for triggering GCX degradation [34]. GCX degradation leads exteriorization of ICAM-1 (intercellular adhesion molecule 1) and/or VCAM-1 (vascular cell adhesion molecule 1) to the lumen of vasculature, which enhances leukocyte-endothelial interactions [35, 36]. The rolling leukocyte on the vessel wall is visualized in the septic model where the leukocyte is labeled with rhodamine 6G (Fig. 3a).Fig. 3

View Article: PubMed Central - PubMed

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.

No MeSH data available.