Shedding of the Vascular Endothelial Glycocalyx: A Common Pathway to Severe Malaria?

2019 ◽  
Vol 69 (10) ◽  
pp. 1721-1723
Author(s):  
Athina Georgiadou ◽  
Aubrey J Cunnington
2020 ◽  
Vol 21 (2) ◽  
pp. 176-183
Author(s):  
Kai Erik Swenson ◽  
Marc Moritz Berger ◽  
Mahdi Sareban ◽  
Franziska Macholz ◽  
Peter Schmidt ◽  
...  

2019 ◽  
Vol 6 (6) ◽  
pp. 190607 ◽  
Author(s):  
P. Sáez ◽  
D. Gallo ◽  
U. Morbiducci

The glycocalyx has been identified as a key mechano-sensor of the shear forces exerted by streaming blood onto the vascular endothelial lining. Although the biochemical reaction to the blood flow has been extensively studied, the mechanism of transmission of the haemodynamic shear forces to the endothelial transmembrane anchoring structures and, consequently, to the subcellular elements in the cytoskeleton, is still not fully understood. Here we apply a multiscale approach to elucidate how haemodynamic shear forces are transmitted to the transmembrane anchors of endothelial cells. Wall shear stress time histories, as obtained from image-based computational haemodynamics models of a carotid bifurcation, are used as a load and a continuum model is applied to obtain the mechanical response of the glycocalyx all along the cardiac cycle. The main findings of this in silico study are that: (1) the forces transmitted to the transmembrane anchors are in the range of 1–10 pN, which is in the order of magnitude reported for the different conformational states of transmembrane mechanotranductors; (2) locally, the forces transmitted to the anchors of the glycocalyx structure can be markedly different from the near-wall haemodynamic shear forces both in amplitude and frequency content. The findings of this in silico approach warrant future studies focusing on the actual forces transmitted to the transmembrane mechanotransductors, which might outperform haemodynamic descriptors of disturbed shear as localizing factors of vascular disease.


2019 ◽  
Vol 88 (3) ◽  
Author(s):  
Eric Lyimo ◽  
Lars Emil Haslund ◽  
Thomas Ramsing ◽  
Christian William Wang ◽  
Akinwale Michael Efunshile ◽  
...  

ABSTRACT Severe malaria is mostly caused by Plasmodium falciparum, resulting in considerable, systemic inflammation and pronounced endothelial activation. The endothelium forms an interface between blood and tissue, and vasculopathy has previously been linked with malaria severity. We studied the extent to which the endothelial glycocalyx that normally maintains endothelial function is involved in falciparum malaria pathogenesis by using incident dark-field imaging in the buccal mucosa. This enabled calculation of the perfused boundary region, which indicates to what extent erythrocytes can permeate the endothelial glycocalyx. The perfused boundary region was significantly increased in severe malaria patients and mirrored by an increase of soluble glycocalyx components in plasma. This is suggestive of a substantial endothelial glycocalyx loss. Patients with severe malaria had significantly higher plasma levels of sulfated glycosaminoglycans than patients with uncomplicated malaria, whereas other measured glycocalyx markers were raised to a comparable extent in both groups. In severe malaria, the plasma level of the glycosaminoglycan hyaluronic acid was positively correlated with the perfused boundary region in the buccal cavity. Plasma hyaluronic acid and heparan sulfate were particularly high in severe malaria patients with a low Blantyre coma score, suggesting involvement in its pathogenesis. In vivo imaging also detected perivascular hemorrhages and sequestering late-stage parasites. In line with this, plasma angiopoietin-1 was decreased while angiopoietin-2 was increased, suggesting vascular instability. The density of hemorrhages correlated negatively with plasma levels of angiopoietin-1. Our findings indicate that as with experimental malaria, the loss of endothelial glycocalyx is associated with vascular dysfunction in human malaria and is related to severity.


2021 ◽  
Vol 8 ◽  
Author(s):  
Keigo Kusuzawa ◽  
Keiko Suzuki ◽  
Hideshi Okada ◽  
Kodai Suzuki ◽  
Chihiro Takada ◽  
...  

Glycocalyx is present on the surface of healthy endothelium, and the concentration of serum syndecan-1 can serve as an injury marker. This study aimed to assess endothelial injury using serum syndecan-1 as a marker of endothelial glycocalyx injury in patients who underwent hemodialysis. In this single-center, retrospective, observational study, 145 patients who underwent hemodialysis at the Gifu University Hospital between March 2017 and December 2019 were enrolled. The median dialysis period and time were 63 months and 3.7 h, respectively. The serum syndecan-1 concentration significantly increased from 124.6 ± 107.8 ng/ml before hemodialysis to 229.0 ± 138.1 ng/ml after hemodialysis (P < 0.001). Treatment with anticoagulant nafamostat mesylate inhibited hemodialysis-induced increase in the levels of serum syndecan-1 in comparison to unfractionated heparin. Dialysis time and the change in the syndecan-1 concentration were positively correlated. Conversely, the amount of body fluid removed and the changes in the syndecan-1 concentration were not significantly correlated. The reduction in the amount of body fluid removed and dialysis time inhibited the change in the syndecan-1 levels before and after hemodialysis. In conclusion, quantitative assessment of the endothelial glycocalyx injury during hemodialysis can be performed by measuring the serum syndecan-1 concentration, which may aid in the selection of appropriate anticoagulants, reduction of hemodialysis time, and the amount of body fluid removed.


Author(s):  
Charles S. Wallace ◽  
Tobias Hasenberg ◽  
Morton H. Friedman

The endothelial glycocalyx is believed to play a crucial role in many endothelial functions, including mechanotransduction [1,2], modulation of vascular permeability, and interaction with blood components [3]. A principal constituent of the glycocalyx, thought to sense shearing forces and convey this signal into the cell, is the glycosaminoglycan heparan sulfate (HS). Previous in vitro studies have shown that batch removal of 60% of the heparan sulfate within the glycocalyx inhibits the steady shear-induced production of nitric oxide [4], cell alignment, cell migration, suppression of cell proliferation, and accumulation of vascular endothelial cadherin in cell-cell junctions [5].


Shock ◽  
2021 ◽  
Vol 56 (4) ◽  
pp. 593-600 ◽  
Author(s):  
Sang Kien Truong ◽  
Takasumi Katoh ◽  
Soichiro Mimuro ◽  
Tsunehisa Sato ◽  
Kensuke Kobayashi ◽  
...  

2018 ◽  
Vol 22 (2) ◽  
Author(s):  
Maria Pikoula ◽  
Matthew B. Tessier ◽  
Robert J. Woods ◽  
Yiannis Ventikos

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