Abstract | INTRODUCTION: The angiogenic proteins angiopoietin (Ang)-1, Ang-2 and vascular endothelial growth factor ( VEGF) are regulators of endothelial inflammation and integrity. Since platelets store large amounts of Ang-1 and VEGF, measurement of circulation levels of these proteins is sensitive to platelet number, in vivo platelet activation and inadvertent platelet activation during blood processing. We studied plasma Ang-1, Ang-2 and VEGF levels in malaria patients, taking the necessary precautions to avoid ex vivo platelet activation, and related plasma levels to platelet count and the soluble platelet activation markers P-selectin and CXCL7. METHODS: Plasma levels of Ang-1, Ang-2, VEGF, P-selectin and CXCL7 were measured in CTAD plasma, minimizing ex vivo platelet activation, in 27 patients with febrile Plasmodium falciparum malaria at presentation and day 2 and 5 of treatment and in 25 healthy controls. RESULTS: Levels of Ang-1, Ang-2 and VEGF were higher at day 0 in malaria patients compared to healthy controls. Ang-2 levels, which is a marker of endothelial activation, decreased after start of antimalarial treatment. In contrast, Ang-1 and VEGF plasma levels increased and this corresponded with the increase in platelet number. Soluble P-selectin and CXCL7 levels followed the same trend as Ang-1 and VEGF levels. Plasma levels of these four proteins correlated strongly in malaria patients, but only moderately in controls. CONCLUSION: In contrast to previous studies, we found elevated plasma levels of Ang-1 and VEGF in patients with malaria resulting from in vivo platelet activation. Ang-1 release from platelets may be important to dampen the disturbing effects of Ang-2 on the endothelium. Evaluation of plasma levels of these angiogenic proteins requires close adherence to a stringent protocol to minimize ex vivo platelet activation.
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Authors | Judith Brouwers, Rintis Noviyanti, Rob Fijnheer, Philip G de Groot, Leily Trianty, Siti Mudaliana, Mark Roest, Din Syafruddin, Andre van der Ven, Quirijn de Mast |
Journal | PloS one
(PLoS One)
Vol. 8
Issue 6
Pg. e64850
( 2014)
ISSN: 1932-6203 [Electronic] United States |
PMID | 23755151
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- ANGPT1 protein, human
- Angiopoietin-1
- Biomarkers
- VEGFA protein, human
- Vascular Endothelial Growth Factor A
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Topics |
- Adolescent
- Adult
- Angiopoietin-1
(blood)
- Biomarkers
(blood)
- Case-Control Studies
- Child
- Female
- Humans
- Malaria
(blood)
- Male
- Platelet Activation
- Platelet Count
- Statistics, Nonparametric
- Vascular Endothelial Growth Factor A
(blood)
- Young Adult
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