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Mediators of Inflammation
Volume 2013, Article ID 174168, 8 pages
http://dx.doi.org/10.1155/2013/174168
Research Article

Attenuation of Myocardial Injury by HMGB1 Blockade during Ischemia/Reperfusion Is Toll-Like Receptor 2-Dependent

1Department of Anaesthesia, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany
2Department of Trauma Surgery, University Hospital Gießen and Marburg GmbH, 35043 Marburg, Germany
3Institute for Microbiology and Hygiene, Charité Medical Center, 12203 Berlin, Germany

Received 29 August 2013; Revised 23 October 2013; Accepted 4 November 2013

Academic Editor: Stefanie B. Flohé

Copyright © 2013 Jan Mersmann et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.