Glycocalyx Special Edition

The American Journal of Pathology Special edition opens with an overview of nanomechanics; the connections between the luminal surface endothelial glycocalyx and the intra-endothelial cortex, largely composed of actin molecules, is emphasised. The sequelae of endothelial glycocalyx injury include enhanced vascular permeability, tissue oedema, augmented leukocyte adhesion, platelet aggregation, and dysregulated vasodilation. The structure/ function of the glycocalyx-cortex unit which regulates many intracellular pathways must be implicated in this pathophysiology.

The second contribution is from the Renal Unit, Bristol and examines The Pathological Relevance of Increased Endothelial Glycocalyx Permeability. Unsurprisingly it emphasises the glomerular capillary glycoclayx which overhangs the large open fenestrations that permit a phenomenal filtration rate – the glomerular filtration rate – from plasma to the tubular fluid. It is tempting to equate the degree of albuminuria with glycocalyx injury, but other factors are at play.

The third paper associates glycocalyx and ischaemia / repercussion pathophysiology; Glycocalyx Degradation in Ischemia-Reperfusion Injury. The researchers share a common theme that heparan sulfate and syndecan-1 are glycocalyx constituent molecules whose increased plasma concentration indicates glycocalyx ‘shedding’.

The fourth review gives us a Focus on Hyaluronan Shedding. Readers of Fluid Physiology will be familiar with my scepticism that we may presume the ubiquitous glycosaminoglycan molecule hyaluronan only rises when the glycocalyx is damaged.

The fifth contribution continues the focus on hyaluronan (HA) as it interests diabetologists; Role in Prevention of Diabetic Complications. The authors explain that the (re)synthesis of HA is dependent on the availability of its sugar substrates, thus linking glycocalyx biology directly to cellular glucose metabolism. 

Last but not least, there is some speculation on glycocalyx turnover in so-called Sepsis and Acute Respiratory Distress Syndrome. Free PMC article so you may enjoy at home, but this series of papers illustrates for me the odd fact that the disease a specialist attributes to fashionable molecules depends primarily on the patients she sees. Renal injury, diabetes and so-called Sepsis are not part of a continuum, they are separate diseases. So how can we be confident that glycocalyx pathophysiology is a sine qua non of any of them? When we see a diagram like the one below, it gives us hope that the science has been established. But reflect again on the first paper in this series; where in the figure below is the intracellular actin-rich cortex that forms a vital functional unit with the glycocalyx? Wither the open fenestration of a glomerular capillary as a transcellular pathway? No sign either of any paracellular filtration through the glycocalyx to the sub-glycocalyx space. From within our own bubble we see what we want to see, and no more. Sadly.

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