Myocardial ischaemia-reperfusion (MIR) triggers a sterile inflammatory response important for myocardial healing, but which may also contribute to adverse ventricular remodelling. Such inflammation is initiated by molecular danger signals released by damaged myocardium, which induce innate immune responses by activating toll-like receptors (TLRs). Detrimental roles have been recently reported for TLR2, TLR3 and TLR4. The role of other TLRs is unknown. We therefore evaluated the role of TLR5, expressed at high level in the heart, in the development of myocardial damage and inflammation acutely triggered by MIR. TLR5−/− and wild-type (WT) mice were exposed to MIR (30 min ischaemia, 2 h reperfusion). We measured infarct size, markers of cardiac oxidative stress, myocardial phosphorylation state of mitogen-activated protein (MAP) kinases and AKT, expression levels of chemokines and cytokines in the heart and plasma, as well as cardiac function by echography and conductance volumetry. TLR5-deficient mice had normal cardiac morphology and function under physiological conditions. After MIR, the absence of TLR5 promoted an increase in infarct size and myocardial oxidative stress. Lack of TLR5 fostered p38 phosphorylation, reduced AKT phosphorylation and markedly increased the expression of inflammatory cytokines, whereas it precipitated acute LV (left ventricle) dysfunction. Therefore, contrary to the detrimental roles of TLR2, TLR3 and TLR4 in the infarcted heart, TLR5 is important to limit myocardial damage, inflammation and functional compromise after MIR.
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Research Article|
April 30 2015
Toll-like receptor 5 deficiency exacerbates cardiac injury and inflammation induced by myocardial ischaemia-reperfusion in the mouse
Roumen Parapanov;
Roumen Parapanov
*Department of Intensive Care Medicine, University Hospital Medical Center and Faculty of Biology and Medicine, Lausanne 1011, Switzerland
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Jérôme Lugrin;
Jérôme Lugrin
*Department of Intensive Care Medicine, University Hospital Medical Center and Faculty of Biology and Medicine, Lausanne 1011, Switzerland
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Nathalie Rosenblatt-Velin;
Nathalie Rosenblatt-Velin
†Division of Clinical Pathophysiology, University Hospital Medical Center and Faculty of Biology and Medicine, Lausanne 2011, Switzerland
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François Feihl;
François Feihl
†Division of Clinical Pathophysiology, University Hospital Medical Center and Faculty of Biology and Medicine, Lausanne 2011, Switzerland
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Bernard Waeber;
Bernard Waeber
†Division of Clinical Pathophysiology, University Hospital Medical Center and Faculty of Biology and Medicine, Lausanne 2011, Switzerland
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Giuseppina Milano;
Giuseppina Milano
‡Service of Cardiac Surgery, University Hospital Medical Center and Faculty of Biology and Medicine, Lausanne 1011, Switzerland
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Catherine Vergely;
Catherine Vergely
§Laboratory of cardio-metabolic pathophysiology and pharmacology, Inserm UMR866, University of Burgundy, Faculty of Medicine and Pharmacy, Dijon 21000, France
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Na Li;
Na Li
§Laboratory of cardio-metabolic pathophysiology and pharmacology, Inserm UMR866, University of Burgundy, Faculty of Medicine and Pharmacy, Dijon 21000, France
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Pal Pacher;
Pal Pacher
║Laboratory of Physiologic Studies, NIH/NIAA, Bethesda 20892-9413, MD, U.S.A.
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Lucas Liaudet
*Department of Intensive Care Medicine, University Hospital Medical Center and Faculty of Biology and Medicine, Lausanne 1011, Switzerland
†Division of Clinical Pathophysiology, University Hospital Medical Center and Faculty of Biology and Medicine, Lausanne 2011, Switzerland
Correspondence: Dr Lucas Liaudet (email: [email protected]).
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Publisher: Portland Press Ltd
Received:
July 24 2014
Revision Received:
February 19 2015
Accepted:
March 11 2015
Accepted Manuscript online:
March 11 2015
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2015 Biochemical Society
2015
Clin Sci (Lond) (2015) 129 (2): 187–198.
Article history
Received:
July 24 2014
Revision Received:
February 19 2015
Accepted:
March 11 2015
Accepted Manuscript online:
March 11 2015
Citation
Roumen Parapanov, Jérôme Lugrin, Nathalie Rosenblatt-Velin, François Feihl, Bernard Waeber, Giuseppina Milano, Catherine Vergely, Na Li, Pal Pacher, Lucas Liaudet; Toll-like receptor 5 deficiency exacerbates cardiac injury and inflammation induced by myocardial ischaemia-reperfusion in the mouse. Clin Sci (Lond) 1 July 2015; 129 (2): 187–198. doi: https://doi.org/10.1042/CS20140444
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