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

Research output: Contribution to journalArticle

Original languageEnglish
Pages (from-to)5015-5035
Number of pages21
JournalJournal of Physiology
Volume595
Issue number15
Early online date1 Aug 2017
DOIs
DateAccepted/In press - 8 May 2017
DateE-pub ahead of print - 1 Aug 2017
DatePublished (current) - Aug 2017

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.

    Research areas

  • Endothelial glycocalyx, Permeability, Sialic acid, Correlative Light and Electron Microscopy

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    Rights statement: This is the final published version of the article (version of record). It first appeared online via Wiley at http://onlinelibrary.wiley.com/doi/10.1113/JP274167/abstract. Please refer to any applicable terms of use of the publisher.

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