FIGURE 1.

Vascular dysfunction in Malaria. Multiple vascular events contribute to malaria pathogenesis and lead to adverse clinical outcomes. The exact mechanism and sequence of events is not known, but early events include endothelial cell activation and rupture of infected RBC. These lead to endothelial glycocalyx breakdown, reduced NO, cellular adhesion and microvascular dysfunction. Endothelial glycocalyx breakdown (shown in the gold, bolded box) is associated with multiple markers of malaria disease severity and may play a central role in different aspects of malaria pathogenesis. ADMA, asymmetric dimethylarginine; Ang-2, angiopoietin-2; BH4, tetrahydrobiopterin; CAMs, cell adhesion molecules; CS, chondroitin sulfate; eGC, endothelial glycocalyx; GAG, glycosaminoglycan; Hb, hemoglobin; HA, hyaluronic acid; HS, heparan sulfate; iRBC, infected red blood cell; NO, nitric oxide; OPG, osteoprotegerin; ROS, reactive oxygen species; S1P, sphingosine-1-phosphate; VWF, von Willebrand factor.