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Shock-Driven Endotheliopathy in Trauma Patients Is Associated with Leucocyte Derived Extracellular Vesicles

Endotheliopathy following trauma is associated with poor outcome, but the underlying mechanisms are unknown. This study hypothesized that an increased extracellular vesicle (EV) concentration is associated with endotheliopathy after trauma and that red blood cell (RBC) transfusion could further enha...

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Autores principales: Dujardin, Romein W. G., Kisters, Jeske E. C., Wirtz, Mathijs R., Hajji, Najat, Tuip-de Boer, Anita M., Stensballe, Jakob, Johansson, Pär I., Brohi, Karim, Davenport, Ross A., Gaarder, Christine, Stanworth, Simon, Maegele, Marc, Nieuwland, Rienk, van der Pol, Edwin, Juffermans, Nicole P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9782606/
https://www.ncbi.nlm.nih.gov/pubmed/36555630
http://dx.doi.org/10.3390/ijms232415990
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author Dujardin, Romein W. G.
Kisters, Jeske E. C.
Wirtz, Mathijs R.
Hajji, Najat
Tuip-de Boer, Anita M.
Stensballe, Jakob
Johansson, Pär I.
Brohi, Karim
Davenport, Ross A.
Gaarder, Christine
Stanworth, Simon
Maegele, Marc
Nieuwland, Rienk
van der Pol, Edwin
Juffermans, Nicole P.
author_facet Dujardin, Romein W. G.
Kisters, Jeske E. C.
Wirtz, Mathijs R.
Hajji, Najat
Tuip-de Boer, Anita M.
Stensballe, Jakob
Johansson, Pär I.
Brohi, Karim
Davenport, Ross A.
Gaarder, Christine
Stanworth, Simon
Maegele, Marc
Nieuwland, Rienk
van der Pol, Edwin
Juffermans, Nicole P.
author_sort Dujardin, Romein W. G.
collection PubMed
description Endotheliopathy following trauma is associated with poor outcome, but the underlying mechanisms are unknown. This study hypothesized that an increased extracellular vesicle (EV) concentration is associated with endotheliopathy after trauma and that red blood cell (RBC) transfusion could further enhance endotheliopathy. In this post hoc sub study of a multicentre observational trial, 75 trauma patients were stratified into three groups based on injury severity score or shock. In patient plasma obtained at hospital admission and after transfusion of four RBC transfusions, markers for endotheliopathy were measured and EVs were labelled with anti CD41 (platelet EVs), anti CD235a (red blood cell EVs), anti CD45 (leucocyte EVs), anti CD144 (endothelial EVs) or anti CD62e (activated endothelial EVs) and EV concentrations were measured with flow cytometry. Statistical analysis was performed by a Kruskall Wallis test with Bonferroni correction or Wilcoxon rank test for paired data. In patients with shock, syndecan-1 and von Willebrand Factor (vWF) were increased compared to patients without shock. Additionally, patients with shock had increased red blood cell EV and leucocyte EV concentrations compared to patients without shock. Endotheliopathy markers correlated with leucocyte EVs (ρ = 0.263, p = 0.023), but not with EVs derived from other cells. Injury severity score had no relation with EV release. RBC transfusion increased circulating red blood cell EVs but did not impact endotheliopathy. In conclusion, shock is (weakly) associated with EVs from leucocytes, suggesting an immune driven pathway mediated (at least in part) by shock.
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spelling pubmed-97826062022-12-24 Shock-Driven Endotheliopathy in Trauma Patients Is Associated with Leucocyte Derived Extracellular Vesicles Dujardin, Romein W. G. Kisters, Jeske E. C. Wirtz, Mathijs R. Hajji, Najat Tuip-de Boer, Anita M. Stensballe, Jakob Johansson, Pär I. Brohi, Karim Davenport, Ross A. Gaarder, Christine Stanworth, Simon Maegele, Marc Nieuwland, Rienk van der Pol, Edwin Juffermans, Nicole P. Int J Mol Sci Article Endotheliopathy following trauma is associated with poor outcome, but the underlying mechanisms are unknown. This study hypothesized that an increased extracellular vesicle (EV) concentration is associated with endotheliopathy after trauma and that red blood cell (RBC) transfusion could further enhance endotheliopathy. In this post hoc sub study of a multicentre observational trial, 75 trauma patients were stratified into three groups based on injury severity score or shock. In patient plasma obtained at hospital admission and after transfusion of four RBC transfusions, markers for endotheliopathy were measured and EVs were labelled with anti CD41 (platelet EVs), anti CD235a (red blood cell EVs), anti CD45 (leucocyte EVs), anti CD144 (endothelial EVs) or anti CD62e (activated endothelial EVs) and EV concentrations were measured with flow cytometry. Statistical analysis was performed by a Kruskall Wallis test with Bonferroni correction or Wilcoxon rank test for paired data. In patients with shock, syndecan-1 and von Willebrand Factor (vWF) were increased compared to patients without shock. Additionally, patients with shock had increased red blood cell EV and leucocyte EV concentrations compared to patients without shock. Endotheliopathy markers correlated with leucocyte EVs (ρ = 0.263, p = 0.023), but not with EVs derived from other cells. Injury severity score had no relation with EV release. RBC transfusion increased circulating red blood cell EVs but did not impact endotheliopathy. In conclusion, shock is (weakly) associated with EVs from leucocytes, suggesting an immune driven pathway mediated (at least in part) by shock. MDPI 2022-12-15 /pmc/articles/PMC9782606/ /pubmed/36555630 http://dx.doi.org/10.3390/ijms232415990 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Dujardin, Romein W. G.
Kisters, Jeske E. C.
Wirtz, Mathijs R.
Hajji, Najat
Tuip-de Boer, Anita M.
Stensballe, Jakob
Johansson, Pär I.
Brohi, Karim
Davenport, Ross A.
Gaarder, Christine
Stanworth, Simon
Maegele, Marc
Nieuwland, Rienk
van der Pol, Edwin
Juffermans, Nicole P.
Shock-Driven Endotheliopathy in Trauma Patients Is Associated with Leucocyte Derived Extracellular Vesicles
title Shock-Driven Endotheliopathy in Trauma Patients Is Associated with Leucocyte Derived Extracellular Vesicles
title_full Shock-Driven Endotheliopathy in Trauma Patients Is Associated with Leucocyte Derived Extracellular Vesicles
title_fullStr Shock-Driven Endotheliopathy in Trauma Patients Is Associated with Leucocyte Derived Extracellular Vesicles
title_full_unstemmed Shock-Driven Endotheliopathy in Trauma Patients Is Associated with Leucocyte Derived Extracellular Vesicles
title_short Shock-Driven Endotheliopathy in Trauma Patients Is Associated with Leucocyte Derived Extracellular Vesicles
title_sort shock-driven endotheliopathy in trauma patients is associated with leucocyte derived extracellular vesicles
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9782606/
https://www.ncbi.nlm.nih.gov/pubmed/36555630
http://dx.doi.org/10.3390/ijms232415990
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