Nanomechanics of the Endothelial Glycocalyx in Experimental Sepsis
Open Access
- 20 November 2013
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 8 (11), e80905
- https://doi.org/10.1371/journal.pone.0080905
Abstract
The endothelial glycocalyx (eGC), a carbohydrate-rich layer lining the luminal side of the endothelium, regulates vascular adhesiveness and permeability. Although central to the pathophysiology of vascular barrier dysfunction in sepsis, glycocalyx damage has been generally understudied, in part because of the aberrancy of in vitro preparations and its degradation during tissue handling. The aim of this study was to analyze inflammation-induced damage of the eGC on living endothelial cells by atomic-force microscopy (AFM) nanoindentation technique. AFM revealed the existence of a mature eGC on the luminal endothelial surface of freshly isolated rodent aorta preparations ex vivo, as well as on cultured human pulmonary microvascular endothelial cells (HPMEC) in vitro. AFM detected a marked reduction in glycocalyx thickness (266 ± 12 vs. 137 ± 17 nm, PE. coli lipopolysaccharides (LPS)/kg BW i.p.) compared to controls. Corresponding in vitro experiments revealed that sepsis-associated mediators, such as thrombin, LPS or Tumor Necrosis Factor-α alone were sufficient to rapidly decrease eGC thickness (-50%, all P<0.0001) and stiffness (-20% P<0.0001) on HPMEC. In summary, AFM nanoindentation is a promising novel approach to uncover mechanisms involved in deterioration and refurbishment of the eGC in sepsis.Keywords
This publication has 57 references indexed in Scilit:
- Quantification of the endothelial surface glycocalyx on rat and mouse blood vesselsMicrovascular Research, 2012
- Nanomechanics and Sodium Permeability of Endothelial Surface Layer Modulated by Hawthorn Extract WS 1442PLOS ONE, 2012
- Lest we forget the endothelial glycocalyx in sepsisCritical Care, 2012
- Stiffness and heterogeneity of the pulmonary endothelial glycocalyx measured by atomic force microscopyAmerican Journal of Physiology-Lung Cellular and Molecular Physiology, 2011
- Salt overload damages the glycocalyx sodium barrier of vascular endotheliumPflügers Archiv - European Journal of Physiology, 2011
- Composition of the endothelial glycocalyx and its relation to its thickness and diffusion of small solutesMicrovascular Research, 2010
- Atomic force microscopy detects differences in the surface brush of normal and cancerous cellsNature Nanotechnology, 2009
- Potassium softens vascular endothelium and increases nitric oxide releaseProceedings of the National Academy of Sciences of the United States of America, 2009
- A positive fluid balance is associated with a worse outcome in patients with acute renal failureCritical Care, 2008
- Exogenous nitric oxide requires an endothelial glycocalyx to prevent postischemic coronary vascular leak in guinea pig heartsCritical Care, 2008