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Review
. 2020 Apr;190(4):742-751.
doi: 10.1016/j.ajpath.2019.11.015. Epub 2020 Feb 6.

The Pathological Relevance of Increased Endothelial Glycocalyx Permeability

Matthew J Butler  1 , Colin J Down  2 , Rebecca R Foster  2 , Simon C Satchell  2
Affiliations
Review

The Pathological Relevance of Increased Endothelial Glycocalyx Permeability

Matthew J Butler et al. Am J Pathol. 2020 Apr.

Abstract

The endothelial glycocalyx is a vital regulator of vascular permeability. Damage to this delicate layer can result in increased protein and water transit. The clinical importance of albuminuria as a predictor of kidney disease progression and vascular disease has driven research in this area. This review outlines how research to date has attempted to measure the contribution of the endothelial glycocalyx to vessel wall permeability. We discuss the evidence for the role of the endothelial glycocalyx in regulating permeability in discrete areas of the vasculature and highlight the inherent limitations of the data that have been produced to date. In particular, this review emphasizes the difficulties in interpreting urinary albumin levels in early disease models. In addition, the research that supports the view that glycocalyx damage is a key pathologic step in a diverse array of clinical conditions, including diabetic complications, sepsis, preeclampsia, and atherosclerosis, is summarized. Finally, novel methods are discussed, including an ex vivo glomerular permeability assay that enhances the understanding of permeability changes in disease.

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Figures

Figure 1
Figure 1
The glomerular filtration barrier consists of glomerular endothelial cells (GEnCs), the glomerular basement membrane, and podocytes. GEnCs possess numerous transcellular fenestrations, which permit the high hydraulic permeability necessary for filtration, and a glycocalyx, which covers the luminal surface, extending over the fenestrations. Podocytes form a second cellular layer by interdigitating their foot processes, which connect at the slit diaphragms. The glycocalyx is a complex structure that contains core proteoglycans, such as syndecans and glypicans, holding glycosaminoglycans, heparan sulfate, chondroitin sulfate, and hyaluronan to the cell surface. The glycocalyx contributes to the filtration barrier by depleting the filtrated protein concentration before it reaches the fenestrated glomerular endothelial cell surface. The generation of a zone of protein-depleted filtrate adjacent to the luminal membrane of endothelial cells (shown in pink) limits loss of macromolecules from the plasma and reduces the effective oncotic pressure across the endothelial cell body.
Figure 2
Figure 2
A live perfused mouse glomerulus under anesthesia was imaged using multiphoton microscopy. The image was taken 10 minutes after an intravenous bolus of fluorescein isothiocyanate–wheat germ agglutinin. This lectin binds to sialic acid residues within the glycocalyx (labeled green). The plasma within the capillary loops was labeled red with Alexa Flur–conjugated albumin. The dark areas within the capillary loops represent circulating blood cells. The glomerular endothelial glycocalyx is a continuous layer within the glomerular capillaries that contribute to the restriction of macromolecule and water leakage from the glomerulus into the Bowman space. Scale bar = 50 μm.
Figure 3
Figure 3
The double barrier concept. A: In health, both the intact glycocalyx and a tight endothelial monolayer can limit vascular wall permeability to macromolecules (including albumin). B: When damage to the endothelial barrier is limited to the glycocalyx, in areas of the vasculature where a tight cellular monolayer exists, an intact second barrier remains. This tight endothelial monolayer continues to limit macromolecule transit. In such areas, it is currently not possible to directly measure the contribution of the endothelial glycocalyx to the vessel wall permeability. C: When damage affects both the glycocalyx and the permeability of the underlying monolayer, marked increases in the vascular wall permeability will result, but again calculating the relative contribution of the glycocalyx to the vessel wall permeability is not possible. In summary, to directly measure the contribution of the glycocalyx to vessel permeability, vessels that lack a tight endothelial monolayer must be selected until new techniques are developed that can measure macromolecule concentrations in the subglycocalyx space.
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References

    1. Betteridge K.B., Arkill K.P., Neal C.R., Harper S.J., Foster R.R., Satchell S.C., Bates D.O., Salmon A.H.J. Sialic acids regulate microvessel permeability, revealed by novel in vivo studies of endothelial glycocalyx structure and function. J Physiol. 2017;595:5015–5035. - PMC - PubMed
    1. Butler M.J., Ramnath R., Kadoya H., Desposito D., Riquier-Brison A., Ferguson J.K., Onions K.L., Ogier A.S., ElHegni H., Coward R.J., Welsh G.I., Foster R.R., Peti-Peterdi J., Satchell S.C. Aldosterone induces albuminuria via matrix metalloproteinase-dependent damage of the endothelial glycocalyx. Kidney Int. 2019;95:94–107. - PMC - PubMed
    1. Dane M.J., van den Berg B.M., Lee D.H., Boels M.G., Tiemeier G.L., Avramut M.C., van Zonneveld A.J., van der Vlag J., Vink H., Rabelink T.J. A microscopic view on the renal endothelial glycocalyx. Am J Physiol Renal Physiol. 2015;308:F956–F966. - PubMed
    1. Singh A., Satchell S.C., Neal C.R., McKenzie E.A., Tooke J.E., Mathieson P.W. Glomerular endothelial glycocalyx constitutes a barrier to protein permeability. J Am Soc Nephrol. 2007;18:2885–2893. - PubMed
    1. Curry F.R. Microvascular solute and water transport. Microcirculation. 2005;12:17–31. - PubMed

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