Von Willebrand Factor Increases In Experimental Cerebral Malaria But Is Not Essential For Late-Stage Pathogenesis In Mice
JOURNAL OF THROMBOSIS AND HAEMOSTASIS(2020)
摘要
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 BothVwf(+/+)andVwf(-/-)mice were infected withPlasmodium bergheiANKA (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 uponPbANKA infection inVwf(+/+)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 inVwf(-/-)mice compared toVwf(+/+)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 inVwf(+/+)animals. At day 8.5 post-infection, however, clinical ECM features inVwf(-/-)mice were slightly more beneficial than inVwf(+/+)animals. Despite these minor differences, overall survival was not different betweenVwf(-/-)andVwf(+/+)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.
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关键词
cerebral malaria, malaria, Plasmodium bergheiANKA, thrombocytopenia, von Willebrand factor
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