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Updated: Aug 8, 2026
Evaluation of Extracellular Vesicle Function During Malaria Infection
Published on: February 14, 2018
von Willebrand factor propeptide in malaria: evidence of acute endothelial cell activation
Martine J Hollestelle1, Cynthia Donkor, Ebenezer Akrofi Mantey
1Sanquin, Amsterdam, the Netherlands.
Abstract:
The pathogenicity of Plasmodium falciparum is thought to relate to the unique ability of infected erythrocytes to adhere to and subsequently activate the vascular endothelium. To study the state of endothelial activation during falciparum malaria, we measured plasma levels of both von Willebrand factor (VWF) and its propeptide, indices of chronic and acute endothelial cell perturbation, respectively. Results were correlated with clinical and biochemical markers of disease severity, including plasma lactate. Our data show that acute endothelial cell activation is a hallmark of malaria in children, indicated by a significant rise in VWF and VWF propeptide. The highest VWF and propeptide levels were seen in cerebral and non-cerebral severe malaria, and associations found between VWF propeptide level and lactate (P < 0.001). Mean VWF propeptide levels (nmol/l) were in cerebral malaria 33.4, non-cerebral severe malaria 26.3, mild malaria 22.1, non-malaria febrile illness 10.2, and controls 10.1. Differences between patient and control groups were highly significant (P < 0.005). Follow-up of 26 cerebral malaria cases showed that levels of VWF propeptide, but not VWF fell by 24 h, following the clinical course of disease and recovery. These novel findings potentially implicate acute, regulated exocytosis of endothelial cell Weibel-Palade bodies in the pathogenesis of Plasmodium falciparum malaria.
Insights
Acute endothelial cell activation is key in severe malaria, indicated by elevated von Willebrand factor (VWF) and its propeptide. These markers correlate with disease severity and may reveal insights into malaria pathogenesis.
Area of Science:
- Pathology
- Immunology
- Vascular Biology
Background:
- Plasmodium falciparum malaria pathogenicity is linked to infected erythrocyte adhesion and vascular endothelium activation.
- Endothelial cell activation is a critical factor in the pathogenesis of severe malaria.
Purpose of the Study:
- To investigate endothelial activation during falciparum malaria by measuring plasma levels of von Willebrand factor (VWF) and its propeptide.
- To correlate these markers with clinical and biochemical indicators of disease severity, including plasma lactate.
Main Methods:
- Measurement of plasma von Willebrand factor (VWF) and VWF propeptide levels in children with malaria and controls.
- Correlation of VWF and VWF propeptide levels with clinical data and plasma lactate.
- Follow-up measurements in cerebral malaria cases to assess changes over time.
Main Results:
- Acute endothelial cell activation is a hallmark of malaria in children, evidenced by significant increases in VWF and VWF propeptide.
- Highest VWF and propeptide levels were observed in severe malaria (cerebral and non-cerebral).
- VWF propeptide levels showed a strong association with plasma lactate and decreased within 24 hours in cerebral malaria cases, mirroring clinical recovery.
Conclusions:
- Acute endothelial cell activation, indicated by VWF and VWF propeptide, is a significant feature of Plasmodium falciparum malaria.
- These findings suggest a role for regulated exocytosis of endothelial cell Weibel-Palade bodies in malaria pathogenesis.
- VWF propeptide serves as a sensitive biomarker for acute endothelial activation and disease severity in malaria.
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