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A clinicopathological correlation of the expression of the angiopoietin-Tie-2 receptor pathway in the brain of adults with Plasmodium falciparum malaria

Prapansilp, Panote, Medana, Isabelle, Mai, Nguyen Thi Hoan, Day, Nicholas P. J., Phu, Nguyen Hoan, Yeo, Tsin W., Hien, Tran Tinh, White, Nicholas J., Anstey, Nicholas M. and Turner, Gareth D. H. (2013). A clinicopathological correlation of the expression of the angiopoietin-Tie-2 receptor pathway in the brain of adults with Plasmodium falciparum malaria. Malaria Journal,12:1-15.

Document type: Journal Article
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Title A clinicopathological correlation of the expression of the angiopoietin-Tie-2 receptor pathway in the brain of adults with Plasmodium falciparum malaria
Author Prapansilp, Panote
Medana, Isabelle
Mai, Nguyen Thi Hoan
Day, Nicholas P. J.
Phu, Nguyen Hoan
Yeo, Tsin W.
Hien, Tran Tinh
White, Nicholas J.
Anstey, Nicholas M.
Turner, Gareth D. H.
Journal Name Malaria Journal
Publication Date 2013
Volume Number 12
ISSN 1475-2875   (check CDU catalogue  open catalogue search in new window)
Scopus ID 2-s2.0-84873245993
Start Page 1
End Page 15
Total Pages 15
Place of Publication United Kingdom
Publisher BioMed Central Ltd.
HERDC Category C1 - Journal Article (DIISR)
Abstract Background
Plasma angiopoietin (Ang)-2 is associated with disease severity and mortality in adults and children with falciparum malaria. However the mechanism of action of the angiopoietins in fatal malaria is unclear. This study aimed to determine whether the expression of Ang-1 and Ang-2 and their receptor Tie-2 in cerebral endothelial or parenchymal cells was specific to cerebral malaria (CM), correlated with coma or other severe clinical features, and whether plasma and CSF levels of these markers correlated with the clinical and neuropathological features of severe and fatal malaria in Vietnamese adults.

Methods
Immunohistochemistry was performed for Ang-1, Ang-2 and Tie-2 on post-mortem brain tissue from fatal malaria cases and controls. Quantitative ELISA for plasma and cerebrospinal fluid levels of Ang-1, Ang-2 and Tie-2 was done to compare fatal cases with surviving patients from the same study.

Results
Immunohistochemistry revealed significant differences in expression in endothelial and parenchymal cells compared to controls. However there was no significant difference in expression of these markers on endothelial cells, astroglial cells or neurons between CM and non-cerebral malaria cases. Immunostaining of Ang-1, Ang-2 and Tie-2 was also not associated with Plasmodium falciparum-infected erythrocyte sequestration in the brain. However Ang-1 and Ang-2 expression in neurons was significantly correlated with the incidence of microscopic haemorrhages. Plasma levels of Ang-2 and Ang-2/Ang-1 ratio were associated with the number of severe malaria complications and were significant and independent predictors of metabolic acidosis and fatal outcome.

Conclusions
The independent prognostic significance of Ang-2 and the Ang-2/Ang-1 ratio in severe malaria was confirmed, although immunohistochemistry in fatal cases did not reveal increased expression on brain endothelium in cerebral versus non-cerebral cases. Activation of the Ang-Tie-2 pathway in severe malaria is therefore related to acidosis, number of severity criteria and outcome, but is not a specific event in the brain during cerebral malaria.

Keywords Malaria
Human
Plasmodium falciparum
Pathogenesis
Pathology
Cerebral
Angiopoietin
Tie-2 receptor
Immunohistochemistry
Biomarker
Blood brain
DOI http://dx.doi.org/10.1186/1475-2875-12-50   (check subscription with CDU E-Gateway service for CDU Staff and Students  check subscription with CDU E-Gateway in new window)
Additional Notes This is an Open Access article distributed under the terms of the Creative Commons Attribution License 2.0, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Description for Link Link to CC Attribution 2.0 License
URL http://creativecommons.org/licenses/by/2.0/au/legalcode


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