High mobility group box-1 (HMGB1) protein-induced cardioprotection in sheep with acute myocardial infarction

DE LORENZI A; LOCATELLI P; BAUZÁ MR; GIMÉNEZ CS; CUNIBERTI L; CROTTOGINI A; OLEA FD

Barcelona

Congreso; European Society of Cardiology Congress; 2017

European Society of Cardiology

Introduction. In mice with acute myocardial infarction (AMI), administration of High mobility group box-1 protein (HMGB1) has been shown to induce angiogenesis and recruitment of CKit+ cells, improving heart function. However, the effects of HMGB1 in large mammals closer to the human have not been addressed, this being important to develop translational therapies for patients. We thus aimed at evaluating the effect of HMGB1 on left ventricular function and infarct size in an ovine model of AMI.Methods. Four hours after inducing an antero-apical AMI of approximately 15% of the left ventricular (LV) mass, adult Corriedale sheep were randomized to receive intramyocardial 250 µg of HMGB1 or PBS (both groups n=7) in the peri-infarct zone. Echocardiographic assessment of percent LV wall thickening of the peri-infarct septum (%SWTh) and anterior wall (%AWTh) and percent ejection fraction (%EF) was performed at baseline, 3 and 60 days post-AMI. Infarct size at end follow up was measured as percent of the LV endocardial surface. Capillary and arteriolar densities, as well as gene expression were assessed in the peri-infarct zone.Results. As expected, at 3 days after AMI, all indexes decreased significantly with regard to baseline in both groups. At 60 days, %SWTh and %AWTh increased with regard to day 3 in the HMGB1 group (%SWTh: 27.6±16 vs. 10.5±8.9; %AWTh: 35.3%±8.3 vs. 11.5±3.2, both p