Universität zu Köln

Weber, Carolyn, Jenke, Alexander, Chobanova, Vasilena, Yazdanyar, Mariam, Chekhoeva, Agunda, Eghbalzadeh, Kaveh, Lichtenberg, Artur, Wahlers, Thorsten, Akhyari, Payam ORCID: 0000-0002-6452-8678 and Paunel-Goerguelue, Adnana (2019). Targeting of cell-free DNA by DNase I diminishes endothelial dysfunction and inflammation in a rat model of cardiopulmonary bypass. Sci Rep, 9. LONDON: NATURE PUBLISHING GROUP. ISSN 2045-2322

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Abstract

The use of cardiopulmonary bypass (CPB) results in the activation of leukocytes, release of neutrophil extracellular traps (NETs) and severe inflammation. We hypothesize that targeting of circulating cellfree DNA (cfDNA) by DNases might represent a feasible therapeutic strategy to limit CPB-associated side effects. Male Wistar rats (n = 24) underwent CPB with deep hypothermic circulatory arrest (DHCA) and were divided into 3 groups: control (group 1), one i.v. bolus DNase I before CPB start (group 2) and a second DNase I dose before reperfusion (group 3). We found a positive correlation between plasma cfDNA/NETs levels and compromised endothelial vasorelaxation after CPB. DNase I administration significantly diminished plasma cfDNA/NETs levels. Further, a dose-dependent improvement in endothelial function accompanied by significant reduction of circulating intercellular adhesion molecule (ICAM)-1 was observed. Rats of group 3 had significantly reduced plasma IL-6 levels and downregulated expression of adhesion molecules resulting in impaired leukocyte extravasation and reduced MPO activity in lungs. Mechanistically, digestion of NETs by DNase I significantly diminished NETs-dependent upregulation of adhesion molecules in human endothelial cells. Altogether, systemic DNase / administration during CPB efficiently reduced cfDNA/NETs-mediated endothelial dysfunction and inflammation and might represents a promising therapeutic strategy for clinical practice.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Weber, Carolyn UNSPECIFIED UNSPECIFIED UNSPECIFIED Jenke, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Chobanova, Vasilena UNSPECIFIED UNSPECIFIED UNSPECIFIED Yazdanyar, Mariam UNSPECIFIED UNSPECIFIED UNSPECIFIED Chekhoeva, Agunda UNSPECIFIED UNSPECIFIED UNSPECIFIED Eghbalzadeh, Kaveh UNSPECIFIED UNSPECIFIED UNSPECIFIED Lichtenberg, Artur UNSPECIFIED UNSPECIFIED UNSPECIFIED Wahlers, Thorsten UNSPECIFIED UNSPECIFIED UNSPECIFIED Akhyari, Payam UNSPECIFIED orcid.org/0000-0002-6452-8678 UNSPECIFIED Paunel-Goerguelue, Adnana UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-124250
DOI:	10.1038/s41598-019-55863-8
Journal or Publication Title:	Sci Rep
Volume:	9
Date:	2019
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; ACTIVATION; DAMAGE Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/12425