The Structure and Function of the Endothelial Glycocalyx Layer

Weinbaum, Sheldon; Tarbell, John M.; Damiano, Edward R.

doi:10.1146/annurev.bioeng.9.060906.151959

Cited by 986 publications

(959 citation statements)

References 129 publications

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“…It was only in the last two decades that the importance of this layer and its components was confirmed in the pathophysiology of endothelial disruption and sepsis [9]. As yet, there are very few studies reported (many in animal models of sepsis) on these biomarkers and their role in management of sepsis and its resultant hypotension and organ failure.…”

Section: Commentarymentioning

confidence: 99%

Glycocalyx Components in Prognosis of Sepsis - A Commentary

Bhargava¹,

Anand²,

S³

et al. 2017

Immunotherapy

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Objectives: Endothelial glycocalyx shedding has been recognized as a contributor in sepsis pathophysiology. Hence, we attempted to analyse hyaluronan and syndecan (glycocalyx components) as markers of morbidity and prognosis of sepsis by performing serial measurements in these patients. Design and methods:Subjects were community acquired sepsis, severe sepsis and septic shock patients (150) admitted to ICU of our tertiary care hospital and controls were 50 healthy volunteers. Serum concentrations of markers were measured on days 1,3,5,7 of ICU admission. Survival was assessed after 90 days. Statistical analysis was performed by SPSS version 17.Results: Hyaluronan and syndecan levels were significantly elevated in all categories of sepsis patients as compared to controls (p<0.001). Levels of both markers were increased in severe sepsis and septic shock patients as compared to sepsis patient group at all-time points. Hyaluronan and syndecan differentiated survivors from non survivors (p<0.001). Unlike non-survivors, in the survivor group, median hyaluronan and syndecan levels decreased significantly (p<0.001) in subsequent measurements. ROC analysis for the prediction of mortality identified cut-offs of 441 ng/ml and 898 ng/ml for hyaluronan and syndecan, respectively. The specificity and negative predictive values were 90% and 90% for hyaluronan and 86% and 91% for syndecan, respectively. Kaplan Meier curves revealed similar results. Both markers correlated significantly with APACHE II and SOFA scores. Conclusion:These observations indicate that serial measurements of hyaluronan and syndecan are significant prognostic markers for morbidity and survival in sepsis. Further, therapeutic interventional possibilities need to be explored in experimental interventional prospective multi-centre trials.

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Section: Commentarymentioning

confidence: 99%

Glycocalyx Components in Prognosis of Sepsis - A Commentary

Bhargava¹,

Anand²,

S³

et al. 2017

Immunotherapy

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“…One of these functions is the modulation of permeability in water transport across the blood vessel wall for the conditioning of the oncotic pressure in blood plasma. Since little axial flow enters the glycocalyx layer by penetration [1], the importance of evaluating the permeation characteristics in the direction normal to the luminal surface has long been recognized.…”

Section: Introductionmentioning

confidence: 99%

“…In the glycocalyx layer, core protein fibers with a diameter of 10 to 12 nm are aligned normal to the luminal wall and have a length, i.e., a layer thickness, of 150 to 400 nm, which varies among individuals as well as with the blood vessel site. There is a periodicity of approximately 20 nm in both directions along the fibers (spacing of core protein clusters) and parallel to the luminal wall (center-to-center distance of the fibers) [1,2]. Based on these observations, a mathematical model has been proposed.…”

Section: Introductionmentioning

confidence: 99%

Fluid permeability of fibrous layers with finite thickness

Otomo

Sugihara‐Seki

2015

J Biorheol

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The vascular endothelial surface glycocalyx layer consists of fibrous glycoproteins with a thickness of several hundred nanometers to a few microns. The present study focuses on the function of the glycocalyx layer as a modulator of permeability in water transport across the blood vessel wall. A particulate layer model is developed to analyze the fluid permeation through the glycocalyx layer, which has periodic fibrous structures and finite thickness. Theoretical and numerical computations of the permeation resistance across the layer are performed based on the Stokesian dynamics approach. The results show that the resistance near the ends of the layer is affected considerably by the anisotropy of adjacent particle configurations. We describe such an end effect on the permeability in relation to the layer thickness and particle spacing ratio. It is suggested that the variations in thickness or fiber spacing in the glycocalyx layer could significantly alter its fluid permeation properties.

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“…The glycocalyx layer has been described as a mechanosensor and transducer of FSS on ECs [1,5,[25][26][27][28][29][30][31][32][33][34][35][36]. Theoretical models to describe the transmission of force from fluid flow to the surface of cells covered by glycocalyx have revealed & 2014 The Author(s) Published by the Royal Society.…”

Section: Introductionmentioning

confidence: 99%

Shear-induced force transmission in a multicomponent, multicell model of the endothelium

Dabagh

Jalali

Butler

et al. 2014

J. R. Soc. Interface.

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Haemodynamic forces applied at the apical surface of vascular endothelial cells (ECs) provide the mechanical signals at intracellular organelles and through the inter-connected cellular network. The objective of this study is to quantify the intracellular and intercellular stresses in a confluent vascular EC monolayer. A novel three-dimensional, multiscale and multicomponent model of focally adhered ECs is developed to account for the role of potential mechanosensors (glycocalyx layer, actin cortical layer, nucleus, cytoskeleton, focal adhesions (FAs) and adherens junctions (ADJs)) in mechanotransmission and EC deformation. The overriding issue addressed is the stress amplification in these regions, which may play a role in subcellular localization of mechanotransmission. The model predicts that the stresses are amplified 250-600-fold over apical values at ADJs and 175-200-fold at FAs for ECs exposed to a mean shear stress of 10 dyne cm 22 . Estimates of forces per molecule in the cell attachment points to the external cellular matrix and cell-cell adhesion points are of the order of 8 pN at FAs and as high as 3 pN at ADJs, suggesting that direct force-induced mechanotransmission by single molecules is possible in both. The maximum deformation of an EC in the monolayer is calculated as 400 nm in response to a mean shear stress of 1 Pa applied over the EC surface which is in accord with measurements. The model also predicts that the magnitude of the cell-cell junction inclination angle is independent of the cytoskeleton and glycocalyx. The inclination angle of the cell-cell junction is calculated to be 6.68 in an EC monolayer, which is somewhat below the measured value (9.98) reported previously for ECs subjected to 1.6 Pa shear stress for 30 min. The present model is able, for the first time, to cross the boundaries between different length scales in order to provide a global view of potential locations of mechanotransmission.

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The Structure and Function of the Endothelial Glycocalyx Layer

Cited by 986 publications

References 129 publications

Glycocalyx Components in Prognosis of Sepsis - A Commentary

Glycocalyx Components in Prognosis of Sepsis - A Commentary

Fluid permeability of fibrous layers with finite thickness

Shear-induced force transmission in a multicomponent, multicell model of the endothelium

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