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cfDNA correlates with endothelial damage after cardiac surgery with prolonged cardiopulmonary bypass and amplifies NETosis in an intracellular TLR9-independent manner
Cardiopulmonary bypass (CPB) provokes inflammation culminating in organ dysfunction and increased mortality. Recently, neutrophil extracellular traps (NETs) have been found to be involved in a variety of cardiovascular diseases promoting tissue and organ injury. Here, we aimed to elaborate the proin...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5727170/ https://www.ncbi.nlm.nih.gov/pubmed/29234042 http://dx.doi.org/10.1038/s41598-017-17561-1 |
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author | Paunel-Görgülü, Adnana Wacker, Max El Aita, Mouhamed Hassan, Shoreshfan Schlachtenberger, Georg Deppe, Antje Choi, Yeong-Hoon Kuhn, Elmar Mehler, Thorsten O. Wahlers, Thorsten |
author_facet | Paunel-Görgülü, Adnana Wacker, Max El Aita, Mouhamed Hassan, Shoreshfan Schlachtenberger, Georg Deppe, Antje Choi, Yeong-Hoon Kuhn, Elmar Mehler, Thorsten O. Wahlers, Thorsten |
author_sort | Paunel-Görgülü, Adnana |
collection | PubMed |
description | Cardiopulmonary bypass (CPB) provokes inflammation culminating in organ dysfunction and increased mortality. Recently, neutrophil extracellular traps (NETs) have been found to be involved in a variety of cardiovascular diseases promoting tissue and organ injury. Here, we aimed to elaborate the proinflammatory potential of circulating cell-free (cf)DNA in patients undergoing cardiac surgery with CPB. Plasma was collected pre- and postoperatively as well as at d1, d3, d5 and d8 after surgery. At d1, we found circulating cfDNA levels to be significantly increased in patients with prolonged CPB duration (>100 min) when compared to those with shorter CPB times (CPB < 100 min). Increased CPB duration yielded in higher levels of circulating mitochondrial (mt)DNA, soluble thrombomodulin (sCD141) and ICAM-1, reflecting endothelial damage. Positive correlation between cfDNA and sCD141 was demonstrated at all time points. Plasma and cfDNA from patients with CPB > 100 min induced NETs release by neutrophils from healthy donors which was not suppressed by inhibitors of intracellular toll-like receptor (TLR)9. DNA binding to neutrophils’ surface (s)TLR9 has been evidenced. Altogether, we demonstrate that elevated plasma cfDNA might be useful to assess CPB-mediated detrimental effects, including endothelial damage, in cardiac surgical patients with prolonged CPB duration. cfDNA-triggered NETosis is independent of classical TLR9 signaling. |
format | Online Article Text |
id | pubmed-5727170 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-57271702017-12-13 cfDNA correlates with endothelial damage after cardiac surgery with prolonged cardiopulmonary bypass and amplifies NETosis in an intracellular TLR9-independent manner Paunel-Görgülü, Adnana Wacker, Max El Aita, Mouhamed Hassan, Shoreshfan Schlachtenberger, Georg Deppe, Antje Choi, Yeong-Hoon Kuhn, Elmar Mehler, Thorsten O. Wahlers, Thorsten Sci Rep Article Cardiopulmonary bypass (CPB) provokes inflammation culminating in organ dysfunction and increased mortality. Recently, neutrophil extracellular traps (NETs) have been found to be involved in a variety of cardiovascular diseases promoting tissue and organ injury. Here, we aimed to elaborate the proinflammatory potential of circulating cell-free (cf)DNA in patients undergoing cardiac surgery with CPB. Plasma was collected pre- and postoperatively as well as at d1, d3, d5 and d8 after surgery. At d1, we found circulating cfDNA levels to be significantly increased in patients with prolonged CPB duration (>100 min) when compared to those with shorter CPB times (CPB < 100 min). Increased CPB duration yielded in higher levels of circulating mitochondrial (mt)DNA, soluble thrombomodulin (sCD141) and ICAM-1, reflecting endothelial damage. Positive correlation between cfDNA and sCD141 was demonstrated at all time points. Plasma and cfDNA from patients with CPB > 100 min induced NETs release by neutrophils from healthy donors which was not suppressed by inhibitors of intracellular toll-like receptor (TLR)9. DNA binding to neutrophils’ surface (s)TLR9 has been evidenced. Altogether, we demonstrate that elevated plasma cfDNA might be useful to assess CPB-mediated detrimental effects, including endothelial damage, in cardiac surgical patients with prolonged CPB duration. cfDNA-triggered NETosis is independent of classical TLR9 signaling. Nature Publishing Group UK 2017-12-12 /pmc/articles/PMC5727170/ /pubmed/29234042 http://dx.doi.org/10.1038/s41598-017-17561-1 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Paunel-Görgülü, Adnana Wacker, Max El Aita, Mouhamed Hassan, Shoreshfan Schlachtenberger, Georg Deppe, Antje Choi, Yeong-Hoon Kuhn, Elmar Mehler, Thorsten O. Wahlers, Thorsten cfDNA correlates with endothelial damage after cardiac surgery with prolonged cardiopulmonary bypass and amplifies NETosis in an intracellular TLR9-independent manner |
title | cfDNA correlates with endothelial damage after cardiac surgery with prolonged cardiopulmonary bypass and amplifies NETosis in an intracellular TLR9-independent manner |
title_full | cfDNA correlates with endothelial damage after cardiac surgery with prolonged cardiopulmonary bypass and amplifies NETosis in an intracellular TLR9-independent manner |
title_fullStr | cfDNA correlates with endothelial damage after cardiac surgery with prolonged cardiopulmonary bypass and amplifies NETosis in an intracellular TLR9-independent manner |
title_full_unstemmed | cfDNA correlates with endothelial damage after cardiac surgery with prolonged cardiopulmonary bypass and amplifies NETosis in an intracellular TLR9-independent manner |
title_short | cfDNA correlates with endothelial damage after cardiac surgery with prolonged cardiopulmonary bypass and amplifies NETosis in an intracellular TLR9-independent manner |
title_sort | cfdna correlates with endothelial damage after cardiac surgery with prolonged cardiopulmonary bypass and amplifies netosis in an intracellular tlr9-independent manner |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5727170/ https://www.ncbi.nlm.nih.gov/pubmed/29234042 http://dx.doi.org/10.1038/s41598-017-17561-1 |
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