Experimental cerebral malaria is associated with profound loss of both glycan and protein components of the endothelial glycocalyx.
FASEB J
; 33(2): 2058-2071, 2019 02.
Article
em En
| MEDLINE
| ID: mdl-30226810
ABSTRACT
Vascular pathology is central to malaria pathogenesis and associated with severity of disease. We have previously documented shedding of the cerebral endothelial glycocalyx in experimental malaria and hypothesized that this action is implicated in the pathogenesis of cerebral malaria (CM). Quantification and characterization of the intraluminal vascular glycocalyx are technically challenging. Here, we used ferritin labeling, computerized image analysis, and biochemical characterization by using in vivo biotinylation and pull down. Image analysis divided mice with CM and uncomplicated malaria and uninfected control mice into 3 non-overlapping groups. Biochemical assessment of the luminal surface revealed malaria-induced alterations in all components of the glycocalyx in CM. This loss was mirrored in increases of the same components in peripheral blood samples. Corticosteroid treatment protected against CM, reduced inflammation, and prevented glycocalyx loss. Adjunctive antithrombin-3 also prevented glycocalyx loss and significantly reduced CM-associated mortality, as well as reduced local inflammation and prevented blood-brain barrier leakage. In contrast, inhibition of matrix metalloproteases with batimastat had limited effects on the glycocalyx and disease progression. Thus, glycocalyx loss may be associated with malaria pathogenesis and could be targeted by adjunctive treatment.-Hempel, C., Sporring, J., Kurtzhals, J. A. L. Experimental cerebral malaria is associated with profound loss of both glycan and protein components of the endothelial glycocalyx.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Plasmodium berghei
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Polissacarídeos
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Endotélio Vascular
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Plasmodium chabaudi
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Malária Cerebral
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Glicocálix
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article