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

摘要: 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 this study was to identify HMGB1 as an activator signalling during MI/R. C57BL/6 wild-type (WT) TLR2−/−-mice were injected with vehicle, HMGB1, BoxA one hour before ischemia (30 min) and reperfusion (24 hrs). Infarct size, cardiac troponin T, leukocyte infiltration, release, TLR4-, TLR9-, RAGE-expression quantified. plasma levels measured in patients undergoing coronary artery bypass graft (CABG) surgery. antagonist reduced cardiomyocyte necrosis MI/R WT mice, accompanied by infiltration. Injection did, however, increase infarct size animals. In TLR2−/−-hearts, neither nor affected size. No differences RAGE TLR9 expression could be detected, while display increased TLR4 expression. Plasma after CABG surgery carrying a polymorphism (Arg753Gln). We here provide evidence that absence abrogates infarct-sparing effects blockade.