A transplant for rolled-up outer glycocalyx layer?

Last summer I shared with you Fitzroy Curry’s latest view of the endothelial glycocalyx layer as “a layered structure with a dense branch-like inner layer formed from heparan sulfate rich glycoproteins associated with the endothelial cell membrane (extending about 200 nm from the surface) and an outer gel-like layer, which is more porous. The outer layer (up to 1 micron thick) contains adsorbed plasma proteins and other glycosaminoglycans such as hyaluronic acid. The inner layer forms the primary barrier to macromolecules  and the outer layer forms the microstructure limiting access of red cells and leukocytes to endothelial surface.” https://wp.me/p7AsWa-ab

Now we have two pictorial reports from Gifu, Japan, recently for our enlightenment. (1, 2) Both use a rodent / lipopolysaccharide experimental model of so-called sepsis, the first focusing on systemic capillary beds and the second looking at pulmonary capillaries. In the baseline examinations, the lanthanum-labelled glycocalyx (the gelatinous outer layer?) looks like moss (the authors’ description) and is continuous in continuous capillaries, discontinuous in discontinuous capillaries… Of interest here is the way lipopolysaccharide causes the labelled layer of various systemic capillary beds to roll up into balls, leaving some areas apparently denuded. The effect on pulmonary capillaries is very similar. The authors feel the endothelial surface injury may be associated with organ dysfunction; in the pulmonary capillaries, ARDS, in the kidney, kidney injury. And why not? But causal? Who knows. There is evidence that the endothelial cell can take substantial trimming of its gelatinous outer glycocalyx layer and still function. The dramatic appearance may not reflect the severity of endothelial cell injury.

It seemed unlikely to me that one could infuse GAGs and their associated glycoproteins to repair a degraded outer glycocalyx layer. I was delighted to discover that work is proceeding on finding a coating for denuded endothelial cells (EC). It has even been christened with the memorable title of EC-SEAL, consisting of a GAG backbone of dermatan sulfate carrying selectin-binding peptides. (3) Still very much Watch This Space, I shan’t be investing my pension fund in a cure for endothelial injury and dysfunction  just yet!

  1. https://ccforum.biomedcentral.com/articles/10.1186/s13054-017-1841-8#Sec14
  2. Chest 2018 Mar 16. 10.1016/j.chest.2018.03.003
  3. Pharmaceuticals (Basel) 2017 Mar 29. 10:10.3390/ph10020036 (PMID: 28353658)

By admin

after more than a quarter of a century of intensive care medicine consultancy in one of the UK's largest teaching hospitals Dr Woodcock is on a mission to ensure the steady state Starling principle is known and understood by every student and every practitioner.

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