Vascular Dysfunction in Malaria: Understanding the Role of the Endothelial Glycocalyx
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Date
2021
Journal Title
Journal ISSN
Volume Title
Publisher
Front. Cell Dev. Biol.,
Abstract
Malaria caused by Plasmodium falciparum results in over 400,000 deaths annually,
predominantly affecting African children. In addition, non-falciparum species including
vivax and knowlesi cause significant morbidity and mortality. Vascular dysfunction is
a key feature in malaria pathogenesis leading to impaired blood perfusion, vascular
obstruction, and tissue hypoxia. Contributing factors include adhesion of infected RBC
to endothelium, endothelial activation, and reduced nitric oxide formation. Endothelial
glycocalyx (eGC) protects the vasculature by maintaining vessel integrity and regulating
cellular adhesion and nitric oxide signaling pathways. Breakdown of eGC is known to
occur in infectious diseases such as bacterial sepsis and dengue and is associated with
adverse outcomes. Emerging studies using biochemical markers and in vivo imaging
suggest that eGC breakdown occurs during Plasmodium infection and is associated
with markers of malaria disease severity, endothelial activation, and vascular function. In
this review, we describe characteristics of eGC breakdown in malaria and discuss how
these relate to vascular dysfunction and adverse outcomes. Further understanding of
this process may lead to adjunctive therapy to preserve or restore damaged eGC and
reduce microvascular dysfunction and the morbidity/mortality of malaria.
Description
Keywords
Glycocalyx, Malaria, Glycosaminoglycans
Citation
Bush MA, Anstey NM, Yeo TW, Florence SM, Granger DL, Mwaikambo ED and Weinberg JB (2021) Vascular Dysfunction in Malaria: Understanding the Role of the Endothelial Glycocalyx. Front. Cell Dev. Biol. 9:751251.