Attenuation of Myocardial Injury by HMGB1 Blockade during Ischemia/Reperfusion Is Toll-Like Receptor 2-Dependent
Genetic or pharmacological ablation of toll-like receptor 2 (TLR2) protects against myocardial ischemia/reperfusion injury (MI/R). However, the endogenous ligand responsible for TLR2 activation has not yet been detected. The objective of this study was to identify HMGB1 as an activator of TLR2 signa...
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| Format: | Article |
| Language: | English |
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Wiley
2013-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2013/174168 |
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| author | Jan Mersmann Franziska Iskandar Kathrina Latsch Katharina Habeck Vera Sprunck René Zimmermann Ralf R. Schumann Kai Zacharowski Alexander Koch |
| author_facet | Jan Mersmann Franziska Iskandar Kathrina Latsch Katharina Habeck Vera Sprunck René Zimmermann Ralf R. Schumann Kai Zacharowski Alexander Koch |
| author_sort | Jan Mersmann |
| collection | DOAJ |
| description | Genetic or pharmacological ablation of toll-like receptor 2 (TLR2) protects against myocardial ischemia/reperfusion injury (MI/R). However, the endogenous ligand responsible for TLR2 activation has not yet been detected. The objective of this study was to identify HMGB1 as an activator of TLR2 signalling during MI/R. C57BL/6 wild-type (WT) or TLR2−/−-mice were injected with vehicle, HMGB1, or HMGB1 BoxA one hour before myocardial ischemia (30 min) and reperfusion (24 hrs). Infarct size, cardiac troponin T, leukocyte infiltration, HMGB1 release, TLR4-, TLR9-, and RAGE-expression were quantified. HMGB1 plasma levels were measured in patients undergoing coronary artery bypass graft (CABG) surgery. HMGB1 antagonist BoxA reduced cardiomyocyte necrosis during MI/R in WT mice, accompanied by reduced leukocyte infiltration. Injection of HMGB1 did, however, not increase infarct size in WT animals. In TLR2−/−-hearts, neither BoxA nor HMGB1 affected infarct size. No differences in RAGE and TLR9 expression could be detected, while TLR2−/−-mice display increased TLR4 and HMGB1 expression. Plasma levels of HMGB1 were increased MI/R in TLR2−/−-mice after CABG surgery in patients carrying a TLR2 polymorphism (Arg753Gln). We here provide evidence that absence of TLR2 signalling abrogates infarct-sparing effects of HMGB1 blockade. |
| format | Article |
| id | doaj-art-767ef945db1549ab82aa7df514de922f |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-767ef945db1549ab82aa7df514de922f2025-02-03T01:30:08ZengWileyMediators of Inflammation0962-93511466-18612013-01-01201310.1155/2013/174168174168Attenuation of Myocardial Injury by HMGB1 Blockade during Ischemia/Reperfusion Is Toll-Like Receptor 2-DependentJan Mersmann0Franziska Iskandar1Kathrina Latsch2Katharina Habeck3Vera Sprunck4René Zimmermann5Ralf R. Schumann6Kai Zacharowski7Alexander Koch8Department of Anaesthesia, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, GermanyDepartment of Anaesthesia, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, GermanyDepartment of Anaesthesia, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, GermanyDepartment of Anaesthesia, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, GermanyDepartment of Anaesthesia, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, GermanyDepartment of Anaesthesia, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, GermanyInstitute for Microbiology and Hygiene, Charité Medical Center, 12203 Berlin, GermanyDepartment of Anaesthesia, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, GermanyDepartment of Anaesthesia, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, GermanyGenetic or pharmacological ablation of toll-like receptor 2 (TLR2) protects against myocardial ischemia/reperfusion injury (MI/R). However, the endogenous ligand responsible for TLR2 activation has not yet been detected. The objective of this study was to identify HMGB1 as an activator of TLR2 signalling during MI/R. C57BL/6 wild-type (WT) or TLR2−/−-mice were injected with vehicle, HMGB1, or HMGB1 BoxA one hour before myocardial ischemia (30 min) and reperfusion (24 hrs). Infarct size, cardiac troponin T, leukocyte infiltration, HMGB1 release, TLR4-, TLR9-, and RAGE-expression were quantified. HMGB1 plasma levels were measured in patients undergoing coronary artery bypass graft (CABG) surgery. HMGB1 antagonist BoxA reduced cardiomyocyte necrosis during MI/R in WT mice, accompanied by reduced leukocyte infiltration. Injection of HMGB1 did, however, not increase infarct size in WT animals. In TLR2−/−-hearts, neither BoxA nor HMGB1 affected infarct size. No differences in RAGE and TLR9 expression could be detected, while TLR2−/−-mice display increased TLR4 and HMGB1 expression. Plasma levels of HMGB1 were increased MI/R in TLR2−/−-mice after CABG surgery in patients carrying a TLR2 polymorphism (Arg753Gln). We here provide evidence that absence of TLR2 signalling abrogates infarct-sparing effects of HMGB1 blockade.http://dx.doi.org/10.1155/2013/174168 |
| spellingShingle | Jan Mersmann Franziska Iskandar Kathrina Latsch Katharina Habeck Vera Sprunck René Zimmermann Ralf R. Schumann Kai Zacharowski Alexander Koch Attenuation of Myocardial Injury by HMGB1 Blockade during Ischemia/Reperfusion Is Toll-Like Receptor 2-Dependent Mediators of Inflammation |
| title | Attenuation of Myocardial Injury by HMGB1 Blockade during Ischemia/Reperfusion Is Toll-Like Receptor 2-Dependent |
| title_full | Attenuation of Myocardial Injury by HMGB1 Blockade during Ischemia/Reperfusion Is Toll-Like Receptor 2-Dependent |
| title_fullStr | Attenuation of Myocardial Injury by HMGB1 Blockade during Ischemia/Reperfusion Is Toll-Like Receptor 2-Dependent |
| title_full_unstemmed | Attenuation of Myocardial Injury by HMGB1 Blockade during Ischemia/Reperfusion Is Toll-Like Receptor 2-Dependent |
| title_short | Attenuation of Myocardial Injury by HMGB1 Blockade during Ischemia/Reperfusion Is Toll-Like Receptor 2-Dependent |
| title_sort | attenuation of myocardial injury by hmgb1 blockade during ischemia reperfusion is toll like receptor 2 dependent |
| url | http://dx.doi.org/10.1155/2013/174168 |
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