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

Hector A. Cabrera-Fuentes; Marisol Ruiz-Meana; Sakine Simsekyilmaz; Sawa Kostin; Javier Inserte; Mona Saffarzadeh; Sebastian P. Galuska; Vijith Vijayan; Ignasi Barba; Guillermo Barreto; Silvia Fischer; Günter Lochnit; Olga N. Ilinskaya; Eveline Baumgart-Vogt; Andreas Böning; Sandrine Lecour; Derek J. Hausenloy; Elisa A. Liehn; David Garcia-Dorado; Klaus-Dieter Schlüter; Klaus T. Preissner

doi:10.1160/th14-08-0703

Thrombosis and Haemostasis, Inhaltsverzeichnis

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

Authors

Hector A. Cabrera-Fuentes

¹Institute of Biochemistry, Medical School, Justus-Liebig-University, Giessen, Germany

⁵Kazan Federal University, Department of Microbiology, Kazan, Russia
Marisol Ruiz-Meana^*

⁶Hospital Universitari Vall d´Hebron, Laboratorio de Cardiología Experimental, Barcelona, Spain
Sakine Simsekyilmaz^*

⁷Institute of Molecular Cardiovascular Research, RWTH, Aachen, Germany
Sawa Kostin^*

⁸Core Lab for Molecular and Structural Biology, Max-Planck-Institute, Bad Nauheim, Germany
Javier Inserte

⁶Hospital Universitari Vall d´Hebron, Laboratorio de Cardiología Experimental, Barcelona, Spain
Mona Saffarzadeh

¹Institute of Biochemistry, Medical School, Justus-Liebig-University, Giessen, Germany
Sebastian P. Galuska

¹Institute of Biochemistry, Medical School, Justus-Liebig-University, Giessen, Germany
Vijith Vijayan

³Institute of Anatomy and Cell Biology II, Medical School, Justus-Liebig-University, Giessen, Germany
Ignasi Barba

⁶Hospital Universitari Vall d´Hebron, Laboratorio de Cardiología Experimental, Barcelona, Spain
Guillermo Barreto

⁹LOEWE Research Group Lung Cancer Epigenetics, Max-Planck-Institute, Bad Nauheim, Germany
Silvia Fischer

¹Institute of Biochemistry, Medical School, Justus-Liebig-University, Giessen, Germany
Günter Lochnit

¹Institute of Biochemistry, Medical School, Justus-Liebig-University, Giessen, Germany
Olga N. Ilinskaya

⁵Kazan Federal University, Department of Microbiology, Kazan, Russia
Eveline Baumgart-Vogt

³Institute of Anatomy and Cell Biology II, Medical School, Justus-Liebig-University, Giessen, Germany
Andreas Böning

⁴Department of Cardiovascular Surgery, Medical School, Justus-Liebig-University, Giessen, Germany
Sandrine Lecour

¹⁰Hatter Institute for Cardiovascular Research, University of Cape Town, Cape Town, South Africa
Derek J. Hausenloy

¹¹The Hatter Cardiovascular Institute, University College London, London, UK
Elisa A. Liehn

⁷Institute of Molecular Cardiovascular Research, RWTH, Aachen, Germany
David Garcia-Dorado

⁶Hospital Universitari Vall d´Hebron, Laboratorio de Cardiología Experimental, Barcelona, Spain
Klaus-Dieter Schlüter

²Institute of Physiology, Medical School, Justus-Liebig-University, Giessen, Germany
Klaus T. Preissner

¹Institute of Biochemistry, Medical School, Justus-Liebig-University, Giessen, Germany

⁵Kazan Federal University, Department of Microbiology, Kazan, Russia

Abstract

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

Volltext

Referenzen

References
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