Platelet activation determines angiopoietin-1 and VEGF levels in malaria: implications for their use as biomarkers.
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 platele...
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doaj-9c1121de19c94ad3a204130f11944dca2020-11-25T01:56:02ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0186e6485010.1371/journal.pone.0064850Platelet activation determines angiopoietin-1 and VEGF levels in malaria: implications for their use as biomarkers.Judith BrouwersRintis NoviyantiRob FijnheerPhilip G de GrootLeily TriantySiti MudalianaMark RoestDin SyafruddinAndre van der VenQuirijn de MastINTRODUCTION: 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.http://europepmc.org/articles/PMC3670845?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
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 |
spellingShingle |
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 Platelet activation determines angiopoietin-1 and VEGF levels in malaria: implications for their use as biomarkers. PLoS ONE |
author_facet |
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 |
author_sort |
Judith Brouwers |
title |
Platelet activation determines angiopoietin-1 and VEGF levels in malaria: implications for their use as biomarkers. |
title_short |
Platelet activation determines angiopoietin-1 and VEGF levels in malaria: implications for their use as biomarkers. |
title_full |
Platelet activation determines angiopoietin-1 and VEGF levels in malaria: implications for their use as biomarkers. |
title_fullStr |
Platelet activation determines angiopoietin-1 and VEGF levels in malaria: implications for their use as biomarkers. |
title_full_unstemmed |
Platelet activation determines angiopoietin-1 and VEGF levels in malaria: implications for their use as biomarkers. |
title_sort |
platelet activation determines angiopoietin-1 and vegf levels in malaria: implications for their use as biomarkers. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2014-01-01 |
description |
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. |
url |
http://europepmc.org/articles/PMC3670845?pdf=render |
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