title: Toll-like receptor 9 prevents cardiac rupture after myocardial infarction in mice independently of inflammation.
abstract: We have reported that the Toll-like receptor 9 (TLR9) signaling pathway plays an important role in the development of pressure overload-induced inflammatory responses and heart failure. However, its role in cardiac remodeling after myocardial infarction has not been elucidated. TLR9-deficient and control C57Bl/6 wild-type mice were subjected to left coronary artery ligation. The survival rate 14 days postoperation was significantly lower in TLR9-deficient mice than that in wild-type mice with evidence of cardiac rupture in all dead mice. Cardiac magnetic resonance imaging showed no difference in infarct size and left ventricular wall thickness and function between TLR9-deficient and wild-type mice. There were no differences in the number of infiltrating inflammatory cells and the levels of inflammatory cytokine mRNA in infarct hearts between TLR9-deficient and wild-type mice. The number of α-smooth muscle actin (αSMA)-positive myofibroblasts and αSMA/Ki67-double-positive proliferative myofibroblasts was increased in the infarct and border areas in infarct hearts compared with those in sham-operated hearts in wild-type mice, but not in TLR9-deficient mice. The class B CpG oligonucleotide increased the phosphorylation level of NF-κB and the number of αSMA-positive and αSMA/Ki67-double-positive cells and these increases were attenuated by BAY1-7082, an NF-κB inhibitor, in cardiac fibroblasts isolated from wild-type hearts. The CpG oligonucleotide showed no effect on NF-κB activation or the number of αSMA-positive and αSMA/Ki67-double-positive cells in cardiac fibroblasts from TLR9-deficient hearts. Although the TLR9 signaling pathway is not involved in the acute inflammatory response in infarct hearts, it ameliorates cardiac rupture possibly by promoting proliferation and differentiation of cardiac fibroblasts.
authors: Cardiovascular Division, King's College London British Heart Foundation Centre of Research Excellence, London, United Kingdom.
authors: Shigemiki
authors: S
authors: Omiya
authors: Cardiovascular Division, King's College London British Heart Foundation Centre of Research Excellence, London, United Kingdom.
authors: Yosuke
authors: Y
authors: Omori
authors: Cardiovascular Division, King's College London British Heart Foundation Centre of Research Excellence, London, United Kingdom.
authors: Manabu
authors: M
authors: Taneike
authors: Cardiovascular Division, King's College London British Heart Foundation Centre of Research Excellence, London, United Kingdom.
authors: Andrea
authors: A
authors: Protti
authors: Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Japan; and.
authors: Osamu
authors: O
authors: Yamaguchi
authors: Laboratory of Host Defense, WPI Immunology Frontier Research Centre, Osaka University, Suita, Japan.
authors: Shizuo
authors: S
authors: Akira
authors: Cardiovascular Division, King's College London British Heart Foundation Centre of Research Excellence, London, United Kingdom.
authors: Ajay M
authors: AM
authors: Shah
authors: Cardiovascular Division, King's College London British Heart Foundation Centre of Research Excellence, London, United Kingdom.
authors: Kazuhiko
authors: K
authors: Nishida
authors: Cardiovascular Division, King's College London British Heart Foundation Centre of Research Excellence, London, United Kingdom; kinya.otsu@kcl.ac.uk.
authors: Kinya
authors: K
authors: Otsu
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002452:Cell Count; D002454:Cell Differentiation / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics*; D003331:Coronary Vessels / Q000601:surgery; D016207:Cytokines / Q000235:genetics; D005347:Fibroblasts / Q000166:cytology*; D006342:Heart Rupture, Post-Infarction / Q000209:etiology / Q000235:genetics* / Q000276:immunology / Q000401:mortality; D007249:Inflammation; D019394:Ki-67 Antigen / Q000378:metabolism; D008026:Ligation; D055909:Magnetic Field Therapy; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000150:complications / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D058628:Myofibroblasts / Q000166:cytology; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D051217:Toll-Like Receptor 9 / Q000235:genetics*
chemical_list: D000199:Actins; D016207:Cytokines; D019394:Ki-67 Antigen; D016328:NF-kappa B; D012333:RNA, Messenger; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9; C544013:alpha-smooth muscle actin, mouse
keywords: Toll-like receptor 9; cardiac fibroblast; cardiac rupture; inflammation; myocardial infarction