von Willebrand factor propeptide in malaria: evidence of acute endothelial cell activation

Abstract

Summary 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.

Plasmodium falciparum malaria, bilateral sixth cranial nerve palsy and delayed cerebellar ataxia

“…Overproduction of cytokines is associated with the activation of the vascular endothelium, a key component of cerebral malaria but not the only one [18]. The inflammatory cytokines (IL-1, IL-2, IFN-ϒ, and TNF-α) are all required for the development of experimental severe malaria (ESM).…”

Pathogenic mechanisms in Plasmodium falciparum malaria

“…En los pacientes con malaria por P. falciparum se incrementan los niveles séricos de marcadores de activación endotelial, como factor de von Willebrand, quimiocina CXCL8/IL-8, endotelina 1 (ET-1) y angiopoyetina 2, moléculas almacenadas y liberadas de los cuerpos de Webel-Palade de las células endoteliales (35)(36)(37)(38). El aumento de del factor de von Willebrand se asocia con enfermedad grave y sugiere que la exocitosis de los cuerpos de Webel-Palade participa en la patogenia de la malaria, aunque se desconoce el estímulo que activa esta liberación (37).…”

“…El aumento de del factor de von Willebrand se asocia con enfermedad grave y sugiere que la exocitosis de los cuerpos de Webel-Palade participa en la patogenia de la malaria, aunque se desconoce el estímulo que activa esta liberación (37). La angiopoyetina 2 (AGN-2) se encuentra elevada en pacientes con malaria grave en comparación con casos no * Tabla elaborada con base en la revisión de (24) complicados y controles sanos.…”

“…La angiopoyetina 2 (AGN-2) se encuentra elevada en pacientes con malaria grave en comparación con casos no * Tabla elaborada con base en la revisión de (24) complicados y controles sanos. Esta molécula participa en la activación endotelial y aumenta la permeabilidad vascular (38); también se ha observado aumento de ET-1 y la disminución del péptido natriurético de tipo C (36,37). La ET-1 es una molécula vasoconstrictora y amplificadora de la inflamación, mientras el péptido natriurético de tipo C produce relajación vascular y reduce la interacción de leucocitos y plaquetas con el endotelio activado.…”

Degradation of Circulating von Willebrand Factor and Its Regulator ADAMTS13 Implicates Secreted Bacillus anthracis Metalloproteases in Anthrax Consumptive Coagulopathy

“…Its absence or reduced activity results in TP, renal dysfunction, fluctuating neurological symptoms, microangiopathic hemolytic anemia, and fever. Other pathological conditions associated with the increase in the level of circulating ULVWF and/or ADAMTS13 deficiency include infections such as parasitic malaria (22), hemolytic uremic syndrome caused by Escherichia coli O157:H7 (23)(24)(25), and Rocky Mountain spotted fever caused by Rickettsia rickettsii (26,27). However VWF and ADAMTS13 pathologies in anthrax have not been studied.…”