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 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.
Author: | Jan MersmannORCiDGND, Franziska Iskandar, Kathrina LatschORCiDGND, Katharina Habeck, Vera SprunckORCiD, René Zimmermann, Ralf R. Schumann, Kai ZacharowskiORCiDGND, Alexander Koch |
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URN: | urn:nbn:de:hebis:30:3-327788 |
DOI: | https://doi.org/10.1155/2013/174168 |
ISSN: | 1466-1861 |
ISSN: | 0962-9351 |
Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/24371373 |
Parent Title (English): | Mediators of inflammation |
Publisher: | Hindawi Publishing Corp. |
Place of publication: | Sylvania, Ohio |
Document Type: | Article |
Language: | English |
Year of Completion: | 2013 |
Year of first Publication: | 2013 |
Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
Release Date: | 2014/01/23 |
Volume: | 2013 |
Issue: | Article ID 174168 |
Page Number: | 9 |
First Page: | 1 |
Last Page: | 8 |
Note: | Copyright © 2013 Jan Mersmann et al. This is an open access article distributed under the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0/ , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
HeBIS-PPN: | 363411771 |
Institutes: | Medizin / Medizin |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Sammlungen: | Universitätspublikationen |
Licence (German): | Creative Commons - Namensnennung 3.0 |