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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, Steve; Foster, Becky; Satchell, Simon; Bates, David O.; Salmon, Andy

Authors

Kai Betteridge

Kenton Arkill

Chris Neal

Steve Harper

Becky Foster

Simon Satchell

David O. Bates

Andy Salmon



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 timedependent 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.

Journal Article Type Article
Publication Date Aug 1, 2017
Journal Journal of Physiology
Print ISSN 0022-3751
Electronic ISSN 1469-7793
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 595
Issue 15
APA6 Citation Betteridge, K., Arkill, K., Neal, C., Harper, S., Foster, B., Satchell, S., …Salmon, A. (2017). Sialic acids regulate microvessel permeability, revealed by novel in vivo studies of endothelial glycocalyx structure and function. Journal of Physiology, 595(15), https://doi.org/10.1113/JP274167
DOI https://doi.org/10.1113/JP274167
Publisher URL http://onlinelibrary.wiley.com/doi/10.1113/JP274167/abstract
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0


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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0





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