title: Toll-like receptor 5 deficiency exacerbates cardiac injury and inflammation induced by myocardial ischaemia-reperfusion in the mouse.
abstract: 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.
authors.affiliation: *Department of Intensive Care Medicine, University Hospital Medical Center and Faculty of Biology and Medicine, Lausanne 1011, Switzerland.
authors.forename: Roumen
authors.initials: R
authors.lastname: Parapanov
authors.affiliation: *Department of Intensive Care Medicine, University Hospital Medical Center and Faculty of Biology and Medicine, Lausanne 1011, Switzerland.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Lugrin
authors.affiliation: †Division of Clinical Pathophysiology, University Hospital Medical Center and Faculty of Biology and Medicine, Lausanne 2011, Switzerland.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Rosenblatt-Velin
authors.affiliation: †Division of Clinical Pathophysiology, University Hospital Medical Center and Faculty of Biology and Medicine, Lausanne 2011, Switzerland.
authors.forename: François
authors.initials: F
authors.lastname: Feihl
authors.affiliation: †Division of Clinical Pathophysiology, University Hospital Medical Center and Faculty of Biology and Medicine, Lausanne 2011, Switzerland.
authors.forename: Bernard
authors.initials: B
authors.lastname: Waeber
authors.affiliation: ‡Service of Cardiac Surgery, University Hospital Medical Center and Faculty of Biology and Medicine, Lausanne 1011, Switzerland.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Milano
authors.affiliation: §Laboratory of cardio-metabolic pathophysiology and pharmacology, Inserm UMR866, University of Burgundy, Faculty of Medicine and Pharmacy, Dijon 21000, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Vergely
authors.affiliation: §Laboratory of cardio-metabolic pathophysiology and pharmacology, Inserm UMR866, University of Burgundy, Faculty of Medicine and Pharmacy, Dijon 21000, France.
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.affiliation: ║Laboratory of Physiologic Studies, NIH/NIAA, Bethesda 20892-9413, MD, U.S.A.
authors.forename: Pal
authors.initials: P
authors.lastname: Pacher
authors.affiliation: *Department of Intensive Care Medicine, University Hospital Medical Center and Faculty of Biology and Medicine, Lausanne 1011, Switzerland.
authors.forename: Lucas
authors.initials: L
authors.lastname: Liaudet
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005838:Genotype; D007113:Immunity, Innate; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress; D010641:Phenotype; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051198:Toll-Like Receptor 5 / Q000172:deficiency* / Q000235:genetics; D018487:Ventricular Dysfunction, Left / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D016277:Ventricular Function, Left; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D018836:Inflammation Mediators; D051198:Toll-Like Receptor 5; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases