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Thromb Haemost 2014; 112(06): 1110-1119
DOI: 10.1160/th14-08-0703
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

RNase1 prevents the damaging interplay between extracellular RNA and tumour necrosis factor-α in cardiac ischaemia/reperfusion injury

Hector A. Cabrera-Fuentes
1   Institute of Biochemistry, Medical School, Justus-Liebig-University, Giessen, Germany
5   Kazan Federal University, Department of Microbiology, Kazan, Russia
,
Marisol Ruiz-Meana   *
6   Hospital Universitari Vall d´Hebron, Laboratorio de Cardiología Experimental, Barcelona, Spain
,
Sakine Simsekyilmaz   *
7   Institute of Molecular Cardiovascular Research, RWTH, Aachen, Germany
,
Sawa Kostin   *
8   Core Lab for Molecular and Structural Biology, Max-Planck-Institute, Bad Nauheim, Germany
,
Javier Inserte
6   Hospital Universitari Vall d´Hebron, Laboratorio de Cardiología Experimental, Barcelona, Spain
,
Mona Saffarzadeh
1   Institute of Biochemistry, Medical School, Justus-Liebig-University, Giessen, Germany
,
Sebastian P. Galuska
1   Institute of Biochemistry, Medical School, Justus-Liebig-University, Giessen, Germany
,
Vijith Vijayan
3   Institute of Anatomy and Cell Biology II, Medical School, Justus-Liebig-University, Giessen, Germany
,
Ignasi Barba
6   Hospital Universitari Vall d´Hebron, Laboratorio de Cardiología Experimental, Barcelona, Spain
,
Guillermo Barreto
9   LOEWE Research Group Lung Cancer Epigenetics, Max-Planck-Institute, Bad Nauheim, Germany
,
Silvia Fischer
1   Institute of Biochemistry, Medical School, Justus-Liebig-University, Giessen, Germany
,
Günter Lochnit
1   Institute of Biochemistry, Medical School, Justus-Liebig-University, Giessen, Germany
,
Olga N. Ilinskaya
5   Kazan Federal University, Department of Microbiology, Kazan, Russia
,
Eveline Baumgart-Vogt
3   Institute of Anatomy and Cell Biology II, Medical School, Justus-Liebig-University, Giessen, Germany
,
Andreas Böning
4   Department of Cardiovascular Surgery, Medical School, Justus-Liebig-University, Giessen, Germany
,
Sandrine Lecour
10   Hatter Institute for Cardiovascular Research, University of Cape Town, Cape Town, South Africa
,
Derek J. Hausenloy
11   The Hatter Cardiovascular Institute, University College London, London, UK
,
Elisa A. Liehn
7   Institute of Molecular Cardiovascular Research, RWTH, Aachen, Germany
,
David Garcia-Dorado
6   Hospital Universitari Vall d´Hebron, Laboratorio de Cardiología Experimental, Barcelona, Spain
,
Klaus-Dieter Schlüter
2   Institute of Physiology, Medical School, Justus-Liebig-University, Giessen, Germany
,
Klaus T. Preissner
1   Institute of Biochemistry, Medical School, Justus-Liebig-University, Giessen, Germany
5   Kazan Federal University, Department of Microbiology, Kazan, Russia
› Author Affiliations
Further Information

Publication History

Received: 26 August 2014

Accepted after minor revision: 20 September 2014

Publication Date:
29 November 2017 (online)

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Summary

Despite optimal therapy, the morbidity and mortality of patients presenting with an acute myocardial infarction (MI) remain significant, and the initial mechanistic trigger of myocardial “ischaemia/reperfusion (I/R) injury” remains greatly unexplained. Here we show that factors released from the damaged cardiac tissue itself, in particular extracellular RNA (eRNA) and tumour-necrosis-factor α (TNF-α), may dictate I/R injury. In an experimental in vivo mouse model of myocardial I/R as well as in the isolated I/R Langendorff-perfused rat heart, cardiomyocyte death was induced by eRNA and TNF-α. Moreover, TNF-α promoted further eRNA release especially under hypoxia, feeding a vicious cell damaging cycle during I/R with the massive production of oxygen radicals, mitochondrial obstruction, decrease in antioxidant enzymes and decline of cardiomyocyte functions. The administration of RNase1 significantly decreased myocardial infarction in both experimental models. This regimen allowed the reduction in cytokine release, normalisation of antioxidant enzymes as well as preservation of cardiac tissue. Thus, RNase1 administration provides a novel therapeutic regimen to interfere with the adverse eRNA-TNF-α interplay and significantly reduces or prevents the pathological outcome of ischaemic heart disease.

Keywords

Inflammatory mediators - ischaemic heart disease - cytokines - cardiology

* Equal contributions.


 

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