von Willebrand factor increases in experimental cerebral malaria but is not essential for late-stage pathogenesis in mice.

BACKGROUND

Cerebral malaria (CM) is the most severe complication of malaria. Endothelial activation, cytokine release, and vascular obstruction are essential hallmarks of CM. Clinical studies have suggested a link between von Willebrand factor (VWF) and malaria pathology.

OBJECTIVES

To investigate the contribution of VWF in the pathogenesis of experimental cerebral malaria (ECM).

METHODS

Both Vwf and Vwf mice were infected with Plasmodium berghei ANKA (PbANKA) to induce ECM. Alterations of plasma VWF and ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13), platelet count, neurological features, and accumulation of platelets and leukocytes in the brain were examined following infection.

RESULTS

Plasma VWF levels significantly increased upon PbANKA infection in Vwf animals. While ADAMTS13 activity was not affected, high molecular weight VWF multimers disappeared at the end-stage ECM, possibly due to an ongoing hypercoagulability. Although the number of reticulocytes, a preferential target for the parasites, was increased in Vwf mice compared to Vwf mice early after infection, parasitemia levels did not markedly differ between the two groups. Interestingly, Vwf mice manifested overall clinical ECM features similar to those observed in Vwf animals. At day 8.5 post-infection, however, clinical ECM features in Vwf mice were slightly more beneficial than in Vwf animals. Despite these minor differences, overall survival was not different between Vwf and Vwf mice. Similarly, PbANKA-induced thrombocytopenia, leukocyte, and platelet accumulations in the brain were not altered by the absence of VWF.

CONCLUSIONS

Our study suggests that increased VWF concentration is a hallmark of ECM. However, VWF does not have a major influence in modulating late-stage ECM pathogenesis.