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Attenuation of Myocardial Injury by HMGB1 Blockade during Ischemia/Reperfusion Is Toll-Like Receptor 2-Dependent
- Source :
- Mediators of Inflammation, Vol 2013 (2013)
- Publication Year :
- 2013
- Publisher :
- Hindawi Limited, 2013.
-
Abstract
- 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.
Details
- Language :
- English
- ISSN :
- 09629351 and 14661861
- Volume :
- 2013
- Database :
- Directory of Open Access Journals
- Journal :
- Mediators of Inflammation
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.767ef945db1549ab82aa7df514de922f
- Document Type :
- article
- Full Text :
- https://doi.org/10.1155/2013/174168