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Glycocalyx and sepsis-induced alterations in vascular permeability

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Abstract

Endothelial cells line the inner portion of the heart, blood vessels, and lymphatic vessels; a basal membrane of extracellular matrix lines the extraluminal side of endothelial cells. The apical side of endothelial cells is the site for the glycocalyx, which is a complex network of macromolecules, including cell-bound proteoglycans and sialoproteins. Sepsis-associated alterations of this structure may compromise endothelial permeability with associated interstitial fluid shift and generalized edema. Indeed, in sepsis, the glycocalyx acts as a target for inflammatory mediators and leukocytes, and its ubiquitous nature explains the damage of tissues that occurs distant from the original site of infection. Inflammatory-mediated injury to glycocalyx can be responsible for a number of specific clinical effects of sepsis, including acute kidney injury, respiratory failure, and hepatic dysfunction. Moreover, some markers of glycocalyx degradation, such as circulating levels of syndecan or selectins, may be used as markers of endothelial dysfunction and sepsis severity. Although a great deal of experimental evidence shows that alteration of glycocalyx is widely involved in endothelial damage caused by sepsis, therapeutic strategies aiming at preserving its integrity did not significantly improve the outcome of these patients.

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Abbreviations

Ang:

Angiopoietin

ETC:

Endothelial cleft

GAG:

Glycosaminoglycan

ICAM-1:

Intercellular adhesion molecule 1

IL:

Interleukin

LPS:

Lipopolysaccharide

MACR:

Microalbuminuria-urinary creatinine ratio

Piv:

Intracapillar hydrostatic pressure

TEM:

Transmission electron microscopy

TNF-α:

Tumor necrosis factor-alpha

VCAM-1:

Vascular cell adhesion molecule 1

VEGF:

Vascular endothelial growth factor

πis:

interstitial colloid-oncotic pressure

πiv:

intravascular colloid-oncotic pressure

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Acknowledgements

We thank Professor Eleonora Sgambati for her kind collaboration.

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Correspondence to Cosimo Chelazzi.

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Chelazzi, C., Villa, G., Mancinelli, P. et al. Glycocalyx and sepsis-induced alterations in vascular permeability. Crit Care 19, 26 (2015). https://doi.org/10.1186/s13054-015-0741-z

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