Platelet disturbances correlate with endothelial cell activation in uncomplicated Plasmodium vivax malaria

Dos-Santos, J. C. K. et al. (2020) Platelet disturbances correlate with endothelial cell activation in uncomplicated Plasmodium vivax malaria. PLoS Neglected Tropical Diseases, 14(7), e0007656. (doi: 10.1371/journal.pntd.0007656) (PMID:32687542) (PMCID:PMC7392343)

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Abstract

Platelets drive endothelial cell activation in many diseases. However, if this occurs in Plasmodium vivax malaria is unclear. As platelets have been reported to be activated and to play a role in inflammatory response during malaria, we hypothesized that this would correlate with endothelial alterations during acute illness. We performed platelet flow cytometry of PAC-1 and P-selectin. We measured platelet markers (CXCL4, CD40L, P-selectin, Thrombopoietin, IL-11) and endothelial activation markers (ICAM-1, von Willebrand Factor and E-selectin) in plasma with a multiplex-based assay. The values of each mediator were used to generate heatmaps, K-means clustering and Principal Component analysis. In addition, we determined pair-wise Pearson’s correlation coefficients to generate correlation networks. Platelet counts were reduced, and mean platelet volume increased in malaria patients. The activation of circulating platelets in flow cytometry did not differ between patients and controls. CD40L levels (Median [IQ]: 517 [406–651] vs. 1029 [732–1267] pg/mL, P = 0.0001) were significantly higher in patients, while P-selectin and CXCL4 showed a nonsignificant trend towards higher levels in patients. The network correlation approach demonstrated the correlation between markers of platelet and endothelial activation, and the heatmaps revealed a distinct pattern of activation in two subsets of P. vivax patients when compared to controls. Although absolute platelet activation was not strong in uncomplicated vivax malaria, markers of platelet activity and production were correlated with higher endothelial cell activation, especially in a specific subset of patients.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Da Silva Filho, Dr Joao
Creator Roles:
Silva-Filho, J. L.Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Writing – original draft
Authors: Dos-Santos, J. C. K., Silva-Filho, J. L., Judice, C. C., Kayano, A. C. A. V., Aliberti, J., Khouri, R., de Lima, D. S., Nakaya, H., Lacerda, M. V. G., De Paula, E. V., Lopes, S. C. P., and Costa, F. T. M.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:PLoS Neglected Tropical Diseases
Publisher:Public Library of Science
ISSN:1935-2727
ISSN (Online):1935-2735
Published Online:20 July 2020
Copyright Holders:This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose
First Published:First published in PLoS Neglected Tropical Diseases 14(7): e0007656
Publisher Policy:Reproduced under a Creative Commons License

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