Glycocalyx breakdown is increased in African children with cerebral and uncomplicated falciparum malaria
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Date
2019
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
The FASEB Journal
Abstract
Abstract
Cerebral malaria (CM) from Plasmodium falciparum infection is associated with endothelial
dysfunction and parasite sequestration. The glycocalyx (GCX), a carbohydrate‐rich layer lining
the endothelium, is crucial in vascular homeostasis. To evaluate the role of its loss in the
pathogenesis of pediatric CM, we measured GCX degradation in Tanzanian children with World
Health Organization‐defined CM (n = 55), uncomplicated malaria (UM; n = 20), and healthy
controls (HCs; n = 25). Urine GCX breakdown products [glycosaminoglycans (GAGs)] were
quantified using dimethylmethylene blue (DMMB) and liquid chromatography‐tandem mass
spectrometry assays. DMMB‐GAG and mass spectrometry (MS)‐GAG (g/mol creatinine) were
increased in CM and UM compared with HCs (P < 0.001), with no differences in DMMB‐GAG
and MS‐GAG between CM and UM children or between those with and without a fatal outcome.
In CM survivors, urinary GCX DMMB‐GAG normalized by d 3. After adjusting for disease
severity, DMMB‐GAG was significantly associated with parasitemia [partial correlation
coefficient (P
corr
) = 0.34; P = 0.01] and plasma TNF (P
corr
= 0.26; P = 0.04) and inversely with
plasma and urine NO oxidation products [P
corr
= ‐0.31 (P = 0.01) and P
corr
= ‐0.26 (P = 0.03),
respectively]. GCX breakdown is increased in children with falciparum malaria, with similar
elevations in CM and UM. Endothelial GCX degradation may impair endothelial NO production,
exacerbate adhesion‐molecule expression, exposure, and parasite sequestration, and contribute to
malaria pathogenesis
Description
Keywords
Plasmodium falciparum, cerebral malaria, nitric oxide
Citation
Yeo, T.W., Bush, P.A., Chen, Y., Young, S.P., Zhang, H., Millington, D.S., Granger, D.L., Mwaikambo, E.D., Anstey, N.M. and Weinberg, J.B., 2019. Glycocalyx breakdown is increased in African children with cerebral and uncomplicated falciparum malaria. The FASEB Journal, 33(12), pp.14185-14193.