Ablation of Toll-like receptor 9 attenuates myocardial ischemia/reperfusion injury in mice.
In myocardial ischemia/reperfusion injury, the innate immune and subsequent inflammatory responses play a crucial role in the extension of myocardial damage. Toll-like receptor 9 (TLR9) is a critical receptor for recognizing unmethylated CpG motifs that mitochondria contain in their DNA, and induces inflammatory responses. The aim of this study was to elucidate the role of TLR9 in myocardial ischemia/reperfusion injury. Isolated hearts from TLR9-deficient and control wild-type mice were subjected to 35 min of global ischemia, followed by 60 min of reperfusion with Langendorff apparatus. Furthermore, wild-type mouse hearts were infused with DNase I and subjected to ischemia/reperfusion. Ablation of TLR9-mediated signaling pathway attenuates myocardial ischemia/reperfusion injury and inflammatory responses, and digestion of extracellular mitochondrial DNA released from the infarct heart partially improved myocardial ischemia/reperfusion injury with no effect on inflammatory responses. TLR9 could be a therapeutic target to reduce myocardial ischemia/reperfusion injury.
['Kitazume-Taneike|Rika|R|', 'Taneike|Manabu|M|', 'Omiya|Shigemiki|S|', 'Misaka|Tomofumi|T|', 'Nishida|Kazuhiko|K|', 'Yamaguchi|Osamu|O|', 'Akira|Shizuo|S|', 'Shattock|Michael J|MJ|', 'Sakata|Yasushi|Y|', 'Otsu|Kinya|K|']
D000818:Animals D016207:Cytokines D003850:Deoxyribonuclease I D005786:Gene Expression Regulation D006334:Heart Function Tests D018836:Inflammation Mediators D008810:Mice, Inbred C57BL D015428:Myocardial Reperfusion Injury D009336:Necrosis D012333:RNA, Messenger D051217:Toll-Like Receptor 9
Toll-like receptor 9 Myocardial ischemia/reperfusion injury Mitochondrial DNA Inflammation Langendorff-perfused mouse heart