The Pathological Relevance of Increased Endothelial Glycocalyx Permeability

Butler, Matthew; Down, Colin J.; Foster, Rebecca R.; Satchell, Simon C.

doi:10.1016/j.ajpath.2019.11.015

Cited by 80 publications

(90 citation statements)

References 95 publications

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“…It is still considered as the major growth factor regulating vascular permeability in tumors and NV diseases. Features of hyperpermeable blood vessels, such as damage to the glycocalyx lining the inner lumen of endothelial cells, disorganization of cell-cell junctions and the dropout of pericytes and discontinuous endothelial cells, are well-established , Butler et al, 2020. VE-cadherin is a dimeric transmembrane protein that clusters at cell-cell contacts, where it forms complexes with other signaling proteins, such as b-catenin, p120, and plakoglobin (Dejana et al, 2008) (Figure 2).…”

Section: Introductionmentioning

confidence: 99%

Exploration of Oxygen-Induced Retinopathy Model to Discover New Therapeutic Drug Targets in Retinopathies

2020

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Oxygen-induced retinopathy (OIR) is a pure hypoxia-driven angiogenesis model and the most widely used model for ischemic retinopathies, such as retinopathy of prematurity (ROP), proliferative diabetic retinopathy (PDR), and retinal vein occlusion (RVO). OIR model has been used to test new potential anti-angiogenic factors for human diseases. We have recently performed the most comprehensive characterization of OIR by a relatively novel mass spectrometry (MS) technique, sequential window acquisition of all theoretical fragment ion mass spectra (SWATH-MS) proteomics and used genetically modified mice strains to identify novel molecular drug targets in angiogenic retinal diseases. We have confirmed the relevance of the identified molecular targets to human diseases by determining their expression pattern in neovascular membranes obtained from PDR and RVO patients. Based on our results, crystallins were the most prominent proteins induced by early hypoxic environment during the OIR, while actomyosin complex and Filamin A-R-Ras axis, that regulates vascular permeability of the angiogenic blood vessels, stood out at the peak of angiogenesis. Our results have revealed potential new therapeutic targets to address hypoxia-induced pathological angiogenesis and the associated vascular permeability in number of retinal diseases.

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Section: Introductionmentioning

confidence: 99%

Exploration of Oxygen-Induced Retinopathy Model to Discover New Therapeutic Drug Targets in Retinopathies

2020

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“…There is insufficient direct evidence showing that circulating concentrations of glycocalyx components correlate with endothelial injury 2 . Many proposed concepts about glycocalyx function in health and disease are therefore still speculative and controversial and not always backed up by clinical evidence 2,10,11 …”

Section: Vascular Permeability and Transvascular Fluid Fluxmentioning

confidence: 99%

“…The double‐barrier concept stipulates that simultaneous disruption of the endothelial cell barrier and glycocalyx is needed to readily increase vascular permeability. While damage to the glycocalyx alone overlying a tight cellular barrier has minimal effect on permeability, identical glycocalyx damage overlying a leaky cellular monolayer will rapidly increase fluid eflux 11 . The effects of glycocalyx damage therefore depend on the underlying endothelial cell phenotype and vary between and probably also within tissues 11 .…”

Section: Vascular Permeability and Transvascular Fluid Fluxmentioning

confidence: 99%

“…While damage to the glycocalyx alone overlying a tight cellular barrier has minimal effect on permeability, identical glycocalyx damage overlying a leaky cellular monolayer will rapidly increase fluid eflux 11 . The effects of glycocalyx damage therefore depend on the underlying endothelial cell phenotype and vary between and probably also within tissues 11 . When glycocalyx‐dependent permeability changes within the systemic vasculature are studied, it is therefore important to consider how both, glycocalyx structural adaptations and the underlying endothelial cell phenotype, will influence detectable permeability changes 11 …”

Section: Vascular Permeability and Transvascular Fluid Fluxmentioning

confidence: 99%

“…The effects of glycocalyx damage therefore depend on the underlying endothelial cell phenotype and vary between and probably also within tissues 11 . When glycocalyx‐dependent permeability changes within the systemic vasculature are studied, it is therefore important to consider how both, glycocalyx structural adaptations and the underlying endothelial cell phenotype, will influence detectable permeability changes 11 …”

Section: Vascular Permeability and Transvascular Fluid Fluxmentioning

confidence: 99%

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Science‐in‐brief: The role of the glycocalyx in critically ill patients with reference to the horse

Dunkel

2020

Equine Veterinary Journal

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Science-in-brief: The role of the glycocalyx in critically ill patients with reference to the horse The glycocalyx is a gel-like layer covering the luminal surface of vascular endothelial cells. It is comprised of membrane-attached proteoglycans, glycosaminoglycan chains and glycoproteins synthesised by the endothelial cells and adherent plasma proteins. The glycocalyx is essential for maintaining homeostasis in the vasculature. 1 In the healthy state, the glycocalyx regulates vascular permeability, provides anti-coagulant and anti-adhesive effects on the surface of endothelial cells and can shield endothelial cells from oxidative stress. 1,2 Additionally, the glycocalyx senses fluid shear forces and transmits these forces to endothelial cells, initiating nitric oxide-mediated vasorelaxation. Considering these key functions, interest in the glycocalyx has significantly increased in the last decades and damage to this vital layer appears to influence progression and recovery in many disease processes.

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