Role of HMGB1 in ischemia/reperfusion injury in a rat model of myocardial infarction

Myocardial infarction (MI) results from the abrupt interruption of coronary blood flow, leading to ischaemia and cardiac tissue necrosis. High mobility group box 1 (HMGB1), a damage-associated molecular pattern, plays a dual role in MI, offering protection or causing damage depending on the cellular redox status, timing of its activity, and location. The aim of this study was to analyse the effects of an anti-HMGB1 protein on certain biochemical parameters of individual myocardial zones, the infarct zone (IZ), injured zone (INZ), and noninfarct zone (NIZ), after MI. Twelve-week-old male WKY rats were randomly divided into 3 experimental groups: 1. control (sham), 2. MI (MI), and 3. MI plus anti-HMGB1 treatment (MI + aHMGB1). MI was induced via 20-min ligation of the left descending coronary artery and was followed by reperfusion. Anti-HMGB1 (10 μl) was administered before reperfusion. The animals were sacrificed 7 days later. The plasma levels of the cytokines IL-6 and TNF-α were determined with a Bio-Plex Pro Cytokine Kit. Total NO-synthase activity was determined by the conversion of [³H]-arginine to [³H]-citrulline. Protein expression was analysed via Western blotting. Lipid peroxidation was evaluated by determining conjugated diene concentrations in the heart, while collagen content in the left ventricle was quantified by measuring hydroxyproline. Anti-HMGB1 treatment increased both NOS activity and endothelial NOS expression while reducing inducible NOS and NFκB expression. It also decreased plasma IL-6 and TNF-α levels, reduced lipid peroxidation, and lowered collagen content. The anti-HMGB1 protein demonstrated cardioprotection by modulating inflammation and oxidative stress, suggesting its potential as a therapeutic agent for MI and related cardiovascular conditions.