In vivo imaging of the buccal mucosa shows loss of the endothelial glycocalyx and perivascular hemorrhages in pediatric Plasmodium falciparum malaria
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In vivo imaging of the buccal mucosa shows loss of the endothelial glycocalyx and perivascular hemorrhages in pediatric Plasmodium falciparum malaria. / Lyimo, Eric; Haslund, Lars Emil; Ramsing, Thomas; Wang, Christian William; Efunshile, Akinwale Michael; Manjurano, Alphaxard; Makene, Victor; Lusingu, John; Theander, Thor Grundtvig; Kurtzhals, Jørgen Anders Lindholm; Paulsen, Rasmus; Hempel, Casper.
I: Infection and Immunity, Bind 88, Nr. 3, e00679-19, 2020.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - In vivo imaging of the buccal mucosa shows loss of the endothelial glycocalyx and perivascular hemorrhages in pediatric Plasmodium falciparum malaria
AU - Lyimo, Eric
AU - Haslund, Lars Emil
AU - Ramsing, Thomas
AU - Wang, Christian William
AU - Efunshile, Akinwale Michael
AU - Manjurano, Alphaxard
AU - Makene, Victor
AU - Lusingu, John
AU - Theander, Thor Grundtvig
AU - Kurtzhals, Jørgen Anders Lindholm
AU - Paulsen, Rasmus
AU - Hempel, Casper
N1 - Copyright © 2020 American Society for Microbiology.
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
U2 - 10.1128/IAI.00679-19
DO - 10.1128/IAI.00679-19
M3 - Journal article
C2 - 31871101
VL - 88
JO - Infection and Immunity
JF - Infection and Immunity
SN - 0019-9567
IS - 3
M1 - e00679-19
ER -
ID: 236557989