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Sialic acids regulate microvessel permeability, revealed by novel in vivo studies of endothelial glycocalyx structure and function

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Sialic acids regulate microvessel permeability, revealed by novel in vivo studies of endothelial glycocalyx structure and function. / Betteridge, Kai; Arkill, Kenton; Neal, Chris; Harper, Steven; Foster, Becky; Satchell, Simon; Bates, Dave; Salmon, Andy.

In: Journal of Physiology, Vol. 595, No. 15, 08.2017, p. 5015-5035.

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@article{5c213a8f42ec41bb8554a1ab33c93bf5,
title = "Sialic acids regulate microvessel permeability, revealed by novel in vivo studies of endothelial glycocalyx structure and function",
abstract = "The endothelial glycocalyx forms a continuous coat over the luminal surface of all vessels, and regulates multiple vascular functions. The contribution of individual components of the endothelial glycocalyx to one critical vascular function, microvascular permeability, remains unclear. We developed novel, real-time, paired methodologies to study the contribution of sialic acids within the endothelial glycocalyx to the structural and functional permeability properties of the same microvessel in vivo. Single perfused rat mesenteric microvessels were perfused with fluorescent endothelial cell membrane and glycocalyx labels, and imaged with confocal microscopy. A broad range of glycocalyx depth measurements (0.17–3.02μm) were obtained with different labels, imaging techniques and analysis methods. The distance between peak cell membrane and peak glycocalyx label provided the most reliable measure of endothelial glycocalyx anatomy, correlating with paired, numerically smaller values of endothelial glycocalyx depth (0.078±0.016μm) from electron micrographs of the same portion of the same vessel. Disruption of sialic acid residues within the endothelial glycocalyx using neuraminidase perfusion decreased endothelial glycocalyx depth and increased apparent solute permeability to albumin in the same vessels in a time- dependent manner, with changes in all three true vessel wall permeability coefficients (hydraulic conductivity, reflection coefficient, and diffusive solute permeability). These novel technologies expand the range of techniques that permit direct studies of the structure of the endothelial glycocalyx and dependent microvascular functions in vivo, and demonstrate that sialic acid residues within the endothelial glycocalyx are critical regulators of microvascular permeability to both water and albumin.",
keywords = "Endothelial glycocalyx, Permeability, Sialic acid, Correlative Light and Electron Microscopy",
author = "Kai Betteridge and Kenton Arkill and Chris Neal and Steven Harper and Becky Foster and Simon Satchell and Dave Bates and Andy Salmon",
year = "2017",
month = "8",
doi = "10.1113/JP274167",
language = "English",
volume = "595",
pages = "5015--5035",
journal = "Journal of Physiology",
issn = "0022-3751",
publisher = "Wiley",
number = "15",

}

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TY - JOUR

T1 - Sialic acids regulate microvessel permeability, revealed by novel in vivo studies of endothelial glycocalyx structure and function

AU - Betteridge, Kai

AU - Arkill, Kenton

AU - Neal, Chris

AU - Harper, Steven

AU - Foster, Becky

AU - Satchell, Simon

AU - Bates, Dave

AU - Salmon, Andy

PY - 2017/8

Y1 - 2017/8

N2 - The endothelial glycocalyx forms a continuous coat over the luminal surface of all vessels, and regulates multiple vascular functions. The contribution of individual components of the endothelial glycocalyx to one critical vascular function, microvascular permeability, remains unclear. We developed novel, real-time, paired methodologies to study the contribution of sialic acids within the endothelial glycocalyx to the structural and functional permeability properties of the same microvessel in vivo. Single perfused rat mesenteric microvessels were perfused with fluorescent endothelial cell membrane and glycocalyx labels, and imaged with confocal microscopy. A broad range of glycocalyx depth measurements (0.17–3.02μm) were obtained with different labels, imaging techniques and analysis methods. The distance between peak cell membrane and peak glycocalyx label provided the most reliable measure of endothelial glycocalyx anatomy, correlating with paired, numerically smaller values of endothelial glycocalyx depth (0.078±0.016μm) from electron micrographs of the same portion of the same vessel. Disruption of sialic acid residues within the endothelial glycocalyx using neuraminidase perfusion decreased endothelial glycocalyx depth and increased apparent solute permeability to albumin in the same vessels in a time- dependent manner, with changes in all three true vessel wall permeability coefficients (hydraulic conductivity, reflection coefficient, and diffusive solute permeability). These novel technologies expand the range of techniques that permit direct studies of the structure of the endothelial glycocalyx and dependent microvascular functions in vivo, and demonstrate that sialic acid residues within the endothelial glycocalyx are critical regulators of microvascular permeability to both water and albumin.

AB - The endothelial glycocalyx forms a continuous coat over the luminal surface of all vessels, and regulates multiple vascular functions. The contribution of individual components of the endothelial glycocalyx to one critical vascular function, microvascular permeability, remains unclear. We developed novel, real-time, paired methodologies to study the contribution of sialic acids within the endothelial glycocalyx to the structural and functional permeability properties of the same microvessel in vivo. Single perfused rat mesenteric microvessels were perfused with fluorescent endothelial cell membrane and glycocalyx labels, and imaged with confocal microscopy. A broad range of glycocalyx depth measurements (0.17–3.02μm) were obtained with different labels, imaging techniques and analysis methods. The distance between peak cell membrane and peak glycocalyx label provided the most reliable measure of endothelial glycocalyx anatomy, correlating with paired, numerically smaller values of endothelial glycocalyx depth (0.078±0.016μm) from electron micrographs of the same portion of the same vessel. Disruption of sialic acid residues within the endothelial glycocalyx using neuraminidase perfusion decreased endothelial glycocalyx depth and increased apparent solute permeability to albumin in the same vessels in a time- dependent manner, with changes in all three true vessel wall permeability coefficients (hydraulic conductivity, reflection coefficient, and diffusive solute permeability). These novel technologies expand the range of techniques that permit direct studies of the structure of the endothelial glycocalyx and dependent microvascular functions in vivo, and demonstrate that sialic acid residues within the endothelial glycocalyx are critical regulators of microvascular permeability to both water and albumin.

KW - Endothelial glycocalyx

KW - Permeability

KW - Sialic acid

KW - Correlative Light and Electron Microscopy

U2 - 10.1113/JP274167

DO - 10.1113/JP274167

M3 - Article

C2 - 28524373

VL - 595

SP - 5015

EP - 5035

JO - Journal of Physiology

JF - Journal of Physiology

SN - 0022-3751

IS - 15

ER -