Universität zu Köln

Paunel-Goerguelue, Adnana, Wacker, Max, El Aita, Mouhamed, Hassan, Shoreshfan, Schlachtenberger, Georg, Deppe, Antje, Choi, Yeong-Hoon, Kuhn, Elmar, Mehler, Thorsten O. and Wahlers, Thorsten (2017). cfDNA correlates with endothelial damage after cardiac surgery with prolonged cardiopulmonary bypass and amplifies NETosis in an intracellular TLR9-independent manner. Sci Rep, 7. LONDON: NATURE PUBLISHING GROUP. ISSN 2045-2322

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Abstract

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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Paunel-Goerguelue, Adnana UNSPECIFIED UNSPECIFIED UNSPECIFIED Wacker, Max UNSPECIFIED UNSPECIFIED UNSPECIFIED El Aita, Mouhamed UNSPECIFIED UNSPECIFIED UNSPECIFIED Hassan, Shoreshfan UNSPECIFIED UNSPECIFIED UNSPECIFIED Schlachtenberger, Georg UNSPECIFIED UNSPECIFIED UNSPECIFIED Deppe, Antje UNSPECIFIED UNSPECIFIED UNSPECIFIED Choi, Yeong-Hoon UNSPECIFIED UNSPECIFIED UNSPECIFIED Kuhn, Elmar UNSPECIFIED UNSPECIFIED UNSPECIFIED Mehler, Thorsten O. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wahlers, Thorsten UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-207963
DOI:	10.1038/s41598-017-17561-1
Journal or Publication Title:	Sci Rep
Volume:	7
Date:	2017
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	2045-2322
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language NEUTROPHIL EXTRACELLULAR TRAPS; SYSTEMIC INFLAMMATORY RESPONSE; MITOCHONDRIAL-DNA; NUCLEAR-DNA; EXPRESSION; ELEVATION; BACTERIA; RELEASE; STRESS; INJURY Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/20796