Vascular Dysfunction in Malaria: Understanding the Role of the Endothelial Glycocalyx

Frontiers in Cell and Developmental Biology

J. Brice Weinberg¹  Margaret A. Bush²  Salvatore M. Florence³  Esther D. Mwaikambo³  Nicholas M. Anstey⁵  Tsin W. Yeo⁶  Donald L. Granger⁷ 

[1] Duke University School of Medicine and Durham VA Medical Centers, Durham, NC, United States;Duke University School of Nursing and Durham VA Medical Centers, Durham, NC, United States;Hubert Kairuki Memorial University, Dar es Salaam, Tanzania;Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore;Menzies School of Health Research, Charles Darwin University, Darwin, NT, Australia;National Centre for Infectious Diseases, Tan Tock Seng Hospital, Singapore, Singapore;School of Medicine, University of Utah and Salt Lake City VA Medical Centers, Salt Lake City, UT, United States;

关键词: glycocalyx;    malaria;    glycosaminoglycans;    endothelium;    vascular dysfunction;   

DOI  :  10.3389/fcell.2021.751251

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown