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FIGURE 1 Scenarios for degradation of EG. (A) A simplified schema of EG. HA (orange); heparan sulfate (red; dermatan and chondroitin sulfates are not shown.

Published byRalph Tyler Modified over 6 years ago

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Presentation on theme: "FIGURE 1 Scenarios for degradation of EG. (A) A simplified schema of EG. HA (orange); heparan sulfate (red; dermatan and chondroitin sulfates are not shown."— Presentation transcript:

1 FIGURE 1 Scenarios for degradation of EG. (A) A simplified schema of EG. HA (orange); heparan sulfate (red; dermatan and chondroitin sulfates are not shown for clarity). Note that diverse proteins are nested in EG, as those shown, as well as albumin and others (see text). GF, growth factors. (B) Heparanase-induced fragmentation of HS results in a partial degradation of EG. (C) Hyaluronidase-induced breakdown of HA chains results in a partial degradation of EG and an increase in permeability. (D) Sheddases cleave proteoglycans, syndecans and glypicans, resulting in peeling off of the entire EG structure. It should be noted that derangements in each component of EG lead in time to disorganization of other components. Hence, the schema depicts only the initial action of EG-degrading enzymes. Nonetheless, this latter scenario based on the action of sheddases results in a most severe and complete degradation of EG (akin to opening a can). From: Endothelial glycocalyx—the battleground for complications of sepsis and kidney injury Nephrol Dial Transplant. Published online May 23, doi: /ndt/gfx076 Nephrol Dial Transplant | © The Author Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

2 FIGURE 2 AFM nanoindentation. (A) A schematic diagram of the AFM assay
FIGURE 2 AFM nanoindentation. (A) A schematic diagram of the AFM assay. Insert: a picture of the AFM head used for nanoindentation. The blue layer on the cell surface indicates the ESG. (B) Quantification of the thickness and stiffness of EG by AFM nanoindentation. From: Endothelial glycocalyx—the battleground for complications of sepsis and kidney injury Nephrol Dial Transplant. Published online May 23, doi: /ndt/gfx076 Nephrol Dial Transplant | © The Author Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

3 FIGURE 3 Representative STORM-acquired images of anti-HS-labeled EG and vWF distribution in controls and 10 min after LPS. The panels show three-dimensional reconstructed images of cultured endothelial cells stained with antibodies against HS and vWF. Note that preparations were nonpermeabilized so that vWF readily detectable after LPS is located extracellularly. Images display the height of EG and detectability of vWF in controls and 10 min after application of LPS (left panels) and side or top views. Note the readily detectable appearance of vWF 10 min after LPS, where it encroaches into the EG. The sites of detectable vWF also appear to be depleted of HS. From: Endothelial glycocalyx—the battleground for complications of sepsis and kidney injury Nephrol Dial Transplant. Published online May 23, doi: /ndt/gfx076 Nephrol Dial Transplant | © The Author Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

4 FIGURE 4 Schematic representation of a very early patchy loss of EG followed by the propagating innate immune response–driven global loss of EG. Exocytosed cargo molecules are represented in red. From: Endothelial glycocalyx—the battleground for complications of sepsis and kidney injury Nephrol Dial Transplant. Published online May 23, doi: /ndt/gfx076 Nephrol Dial Transplant | © The Author Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

5 FIGURE 5 (A) Whole-body EG volume and (B) survival of mice with the soil model of sepsis (FIP) with and without treatment with sulodexide. *P < 0.05. FIP, fecal-induced peritonitis; SDX, sulodexide; OGT, heparanase inhibitor OGT 2115. From: Endothelial glycocalyx—the battleground for complications of sepsis and kidney injury Nephrol Dial Transplant. Published online May 23, doi: /ndt/gfx076 Nephrol Dial Transplant | © The Author Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

6 FIGURE 6 A hypothetical view of the events linking and perpetuating the pathology of EG and endothelial dysfunction. From: Endothelial glycocalyx—the battleground for complications of sepsis and kidney injury Nephrol Dial Transplant. Published online May 23, doi: /ndt/gfx076 Nephrol Dial Transplant | © The Author Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

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