Electron Microscopic Demonstrations of Filamentous Molecular Sieve Plugs in Capillary Fenestrae

Rostgaard, J.; Qvortrup, Klaus

doi:10.1006/mvre.1996.1987

Cited by 150 publications

(127 citation statements)

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“…Until recently, the fenestrae of the GEnC, a requirement to support the high hydraulic conductivity across the GFB, were considered to be empty; however, scanning EM studies using sophisticated techniques to preserve glycocalyx structure have revealed that the GEnC glycocalyx measures up to 300 nm and covers both the fenestral and the interfenestral domains. 21 Such landmark studies confirm, first, that GEnC, like other microvascular endothelia, are covered with a thick coat of glycocalyx and, second, that the GEnC fenestrations are not empty but contain glycocalyx, which may contribute to the barrier to protein passage.…”

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confidence: 86%

Glomerular Endothelial Glycocalyx Constitutes a Barrier to Protein Permeability

Singh

Satchell

Neal

et al. 2007

Journal of the American Society of Nephrology

244

222

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Glycocalyx, composed of glycoproteins including proteoglycans, coats the luminal surface of the glomerular capillaries. Human heparanase degrades heparan sulphate glycosaminoglycans and is upregulated in proteinuric states. In this study, we analyze the structure of the human glomerular endothelial cell glycocalyx in vitro and examine its functional relevance, especially after treatment with human heparanase. Electron microscopy of conditionally immortalized glomerular endothelial cells revealed a 200-nm thick glycocalyx over the plasma membrane, which was also demonstrated by confocal microscopy. Neuraminidase treatment removed the majority of glycocalyx, reduced trans-endothelial electrical resistance by 59%, and increased albumin flux by 207%. Heparinase III and human heparanase specifically cleaved heparan sulphate: this caused no change in trans-endothelial electrical resistance, but increased the albumin passage across the monolayers by 40% and 39%, respectively. Therefore, we have characterized the glomerular endothelial cell glycocalyx and have shown that it contributes to the barrier to flux of albumin across the cell layer. These results suggest an important role for this glycocalyx in the restriction of glomerular protein passage in vivo and suggest ways in which human heparanase levels may be linked to proteinuria in clinical disease.

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mentioning

confidence: 86%

Glomerular Endothelial Glycocalyx Constitutes a Barrier to Protein Permeability

Singh

Satchell

Neal

et al. 2007

Journal of the American Society of Nephrology

244

222

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“…Using freeze-fracture replica of rare sections where the fracture plane passed parallel to the endothelial surface, they showed that anchoring foci are arranged in a hexagonal array with intercluster spacing of typically 100 nm in the frog capillaries [18]. More recent methods of fixation [19], which preserve the aqueous nature of the glycocalyx, combined with exclusion of fluorescently labelled macromolecules suggest that the glycocalyx and associated adsorbed proteins may extend as much as 0.5 μm into the vessel lumen [12,20].…”

Section: Reflection Coefficient (σ)mentioning

confidence: 99%

A Role for the Endothelial Glycocalyx in Regulating Microvascular Permeability in Diabetes Mellitus

Perrin

Harper

Bates

2007

Cell Biochem Biophys

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Diabetic angiopathy is a major cause of morbidity and mortality in diabetes mellitus. Endothelial dysfunction and associated alterations in blood flow, pressure and permeability are widely accepted phenomena in the diabetic milieu and are understood to lead to microangiopathy. Despite the clinical importance of diabetic microangiopathy, the mechanisms of pathogenesis remain elusive. In particular, much is yet to be understood about the nature of the putative increased permeability with respect to diabetes. Microvessel permeability is intrinsically difficult to measure and a surrogate (solute or solvent flux) is usually reported, the measurement of which is hampered by haemodynamic factors, such as flow rate, hydrostatic pressure gradient, solute concentration and surface area available for exchange. Very few studies describing the measurement of permeability with respect to diabetes have controlled for all these factors. As a result, the nature of the increased microvessel permeability in diabetes mellitus and indeed its causes are poorly understood. Recent studies have shown that hyperglycaemia can alter the glycocalyx structure, and parallel findings have shown that the apparent increase in permeability demonstrated in hyperglycaemia may be due to an increase in the permeability of the vessels to water, and not an increase in protein permeability, an effect attributable to altered glycocalyx. This review focuses on the current understanding of microvascular permeability in terms of the endothelial glycocalyxfibre-matrix theory, those methods used to determine permeability in the context of diabetes, and the more recent developments in our understanding of elevated microvascular permeability in the diabetic circulation.

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“…The fenestrae themselves are too large to effectively sieve macromolecules, which suggests that the barrier properties of the endothelium are derived from the cell coat, or glycocalyx, that fills the fenestrae and extends into the capillary lumen. Special fixation techniques have permitted the glomerular endothelial glycocalyx to be visualized by EM (13), and similar cell coats have been shown to be functionally significant in extrarenal capillaries (14). Evidence that the endothelial glycocalyx may play a role in glomerular size and charge selectivity has been reviewed recently (15).…”

Section: Effects Of Other Structures On Glomerular Permeabilitymentioning

confidence: 99%

What determines glomerular capillary permeability?

Deen¹

2004

J. Clin. Invest.

122

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There have been exciting recent advances in our understanding of the structural and molecular biology of the glomerular slit diaphragm, as described in a report in this issue of the JCI (see the related article beginning on page 1475). These findings, combined with data on the permeability of the basement membrane and evidence that the endothelium may be a more important barrier than often supposed, are allowing a clearer understanding to emerge of how the 3 parts of the glomerular capillary wall jointly determine its functional properties.

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Electron Microscopic Demonstrations of Filamentous Molecular Sieve Plugs in Capillary Fenestrae

Cited by 150 publications

References 0 publications

Glomerular Endothelial Glycocalyx Constitutes a Barrier to Protein Permeability

Glomerular Endothelial Glycocalyx Constitutes a Barrier to Protein Permeability

A Role for the Endothelial Glycocalyx in Regulating Microvascular Permeability in Diabetes Mellitus

What determines glomerular capillary permeability?

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