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Expression of functional tissue factor by neutrophil extracellular traps in culprit artery of acute myocardial infarction

AIMS: Neutrophil extracellular traps (NETs) are chromatin filaments released by activated polymorphonuclear neutrophils (PMNs) and decorated with granule proteins with various properties. Several lines of evidence implicate NETs in thrombosis. The functional significance and the in vivo relevance of...

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Autores principales: Stakos, Dimitrios A., Kambas, Konstantinos, Konstantinidis, Theocharis, Mitroulis, Ioannis, Apostolidou, Eirini, Arelaki, Stella, Tsironidou, Victoria, Giatromanolaki, Alexandra, Skendros, Panagiotis, Konstantinides, Stavros, Ritis, Konstantinos
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4458286/
https://www.ncbi.nlm.nih.gov/pubmed/25660055
http://dx.doi.org/10.1093/eurheartj/ehv007
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author Stakos, Dimitrios A.
Kambas, Konstantinos
Konstantinidis, Theocharis
Mitroulis, Ioannis
Apostolidou, Eirini
Arelaki, Stella
Tsironidou, Victoria
Giatromanolaki, Alexandra
Skendros, Panagiotis
Konstantinides, Stavros
Ritis, Konstantinos
author_facet Stakos, Dimitrios A.
Kambas, Konstantinos
Konstantinidis, Theocharis
Mitroulis, Ioannis
Apostolidou, Eirini
Arelaki, Stella
Tsironidou, Victoria
Giatromanolaki, Alexandra
Skendros, Panagiotis
Konstantinides, Stavros
Ritis, Konstantinos
author_sort Stakos, Dimitrios A.
collection PubMed
description AIMS: Neutrophil extracellular traps (NETs) are chromatin filaments released by activated polymorphonuclear neutrophils (PMNs) and decorated with granule proteins with various properties. Several lines of evidence implicate NETs in thrombosis. The functional significance and the in vivo relevance of NETs during atherothrombosis in humans have not been addressed until now. METHODS AND RESULTS: Selective sampling of thrombotic material and surrounding blood from the infarct-related coronary artery (IRA) and the non-IRA was performed during primary percutaneous revascularization in 18 patients with ST-segment elevation acute myocardial infarction (STEMI). Thrombi isolated from IRA contained PMNs and NETs decorated with tissue factor (TF). Although TF was expressed intracellularly in circulating PMNs of STEMI patients, active TF was specifically exposed by NETs obtained from the site of plaque rupture. Treatment of NET structures with DNase I abolished TF functionality measurement. In vitro treatment of control PMNs with plasma obtained from IRA and non-IRA was further shown to induce intracellular up-regulation of TF but not NET formation. A second step consisting of the interaction between PMNs and thrombin-activated platelets was required for NET generation and subsequent TF exposure. CONCLUSION: The interaction of thrombin-activated platelets with PMNs at the site of plaque rupture during acute STEMI results in local NET formation and delivery of active TF. The notion that NETs represent a mechanism by which PMNs release thrombogenic signals during atherothrombosis may offer novel therapeutic targets.
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spelling pubmed-44582862015-06-08 Expression of functional tissue factor by neutrophil extracellular traps in culprit artery of acute myocardial infarction Stakos, Dimitrios A. Kambas, Konstantinos Konstantinidis, Theocharis Mitroulis, Ioannis Apostolidou, Eirini Arelaki, Stella Tsironidou, Victoria Giatromanolaki, Alexandra Skendros, Panagiotis Konstantinides, Stavros Ritis, Konstantinos Eur Heart J Basic Science AIMS: Neutrophil extracellular traps (NETs) are chromatin filaments released by activated polymorphonuclear neutrophils (PMNs) and decorated with granule proteins with various properties. Several lines of evidence implicate NETs in thrombosis. The functional significance and the in vivo relevance of NETs during atherothrombosis in humans have not been addressed until now. METHODS AND RESULTS: Selective sampling of thrombotic material and surrounding blood from the infarct-related coronary artery (IRA) and the non-IRA was performed during primary percutaneous revascularization in 18 patients with ST-segment elevation acute myocardial infarction (STEMI). Thrombi isolated from IRA contained PMNs and NETs decorated with tissue factor (TF). Although TF was expressed intracellularly in circulating PMNs of STEMI patients, active TF was specifically exposed by NETs obtained from the site of plaque rupture. Treatment of NET structures with DNase I abolished TF functionality measurement. In vitro treatment of control PMNs with plasma obtained from IRA and non-IRA was further shown to induce intracellular up-regulation of TF but not NET formation. A second step consisting of the interaction between PMNs and thrombin-activated platelets was required for NET generation and subsequent TF exposure. CONCLUSION: The interaction of thrombin-activated platelets with PMNs at the site of plaque rupture during acute STEMI results in local NET formation and delivery of active TF. The notion that NETs represent a mechanism by which PMNs release thrombogenic signals during atherothrombosis may offer novel therapeutic targets. Oxford University Press 2015-06-07 2015-02-07 /pmc/articles/PMC4458286/ /pubmed/25660055 http://dx.doi.org/10.1093/eurheartj/ehv007 Text en © The Author 2015. Published by Oxford University Press on behalf of the European Society of Cardiology. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Basic Science
Stakos, Dimitrios A.
Kambas, Konstantinos
Konstantinidis, Theocharis
Mitroulis, Ioannis
Apostolidou, Eirini
Arelaki, Stella
Tsironidou, Victoria
Giatromanolaki, Alexandra
Skendros, Panagiotis
Konstantinides, Stavros
Ritis, Konstantinos
Expression of functional tissue factor by neutrophil extracellular traps in culprit artery of acute myocardial infarction
title Expression of functional tissue factor by neutrophil extracellular traps in culprit artery of acute myocardial infarction
title_full Expression of functional tissue factor by neutrophil extracellular traps in culprit artery of acute myocardial infarction
title_fullStr Expression of functional tissue factor by neutrophil extracellular traps in culprit artery of acute myocardial infarction
title_full_unstemmed Expression of functional tissue factor by neutrophil extracellular traps in culprit artery of acute myocardial infarction
title_short Expression of functional tissue factor by neutrophil extracellular traps in culprit artery of acute myocardial infarction
title_sort expression of functional tissue factor by neutrophil extracellular traps in culprit artery of acute myocardial infarction
topic Basic Science
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4458286/
https://www.ncbi.nlm.nih.gov/pubmed/25660055
http://dx.doi.org/10.1093/eurheartj/ehv007
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