Induction of the vascular endothelial growth factor pathway in the brain of adults with fatal falciparum malaria is a non-specific response to severe disease.

Abstract

AIMS:

Pathological or neuroprotective mechanisms in the brain in severe malaria may arise from microvascular obstruction with malaria-parasitized erythrocytes. This study aimed to investigate the role of hypoxia and induction of the vascular endothelial growth factor (VEGF) pathway in the neuropathophysiology of severe malaria.

METHODS AND RESULTS:

Immunohistochemistry was performed on post mortem brain tissue sections from 20 cases of severe malaria and examined for the expression of transcriptional regulators of VEGF [hypoxia-inducible factor-1 alpha (HIF-1alpha), HIF-2alpha], DEC-1, VEGF, VEGF receptors 1 and 2, and the activated, phosphorylated VEGF receptor 2 (pKDR). HIFs showed limited protein expression and/or translocation to cell nuclei in severe malaria, but DEC-1, which is more stable and regulated by HIF-1alpha, was observed. There was heterogeneous expression of VEGF and its receptors in severe malaria and non-malarial disease controls. pKDR expression on vessels was greater in malaria cases than in controls but did not correlate with parasite sequestration. VEGF uptake by malaria parasites was observed.

CONCLUSIONS:

VEGF and its receptor expression levels in severe malaria reflect a non-specific response to severe systemic disease. Potential manipulation of events at the vasculature by the parasite requires further investigation.

• Authors: Isabelle M Medana, Nicholas P J Day, Rachel Roberts, Navakanit Sachanonta, Helen Turley, Emsri Pongponratn, Tran Tinh Hien, Nicholas J White, Gareth D H Turner
• Journal: Histopathology (Histopathology) Vol. 57 Issue 2 Pg. 282-94 (Aug 2010) ISSN: 1365-2559 [Electronic] England
• PMID: 20716170 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Transcription Factors
• VEGFA protein, human
• Vascular Endothelial Growth Factor A
• Vascular Endothelial Growth Factor Receptor-1
• Vascular Endothelial Growth Factor Receptor-2

Topics

• Adult
• Brain (blood supply, metabolism, parasitology, pathology)
• Case-Control Studies
• Humans
• Immunohistochemistry
• Malaria, Cerebral (metabolism, parasitology, pathology)
• Malaria, Falciparum (metabolism, parasitology, pathology)
• Microvessels (parasitology)
• Transcription Factors (metabolism)
• Vascular Endothelial Growth Factor A (metabolism)
• Vascular Endothelial Growth Factor Receptor-1 (metabolism)
• Vascular Endothelial Growth Factor Receptor-2 (metabolism)