High dose intramyocardial hmgb1 protein induces cardiomyogenesis and preserves ventricular function in sheep with acute myocardial infarction

BAUZÁ, MARÍA DEL ROSARIO; DE LORENZI, ANDREA; CROTTOGINI, ALBERTO; GIMÉNEZ, CARLOS SEBASTIÁN; CUNIBERTI, LUIS; LOCATELLI, PAOLA; HNATIUK, ANNA; OLEA, FERNANDA DANIELA

Mar del Plata

Congreso; Reunión Anual de la Sociedad Argentina de Investigación Clínica; 2018

SAIC-SAI-SAFIS

Aims. In rodents with acute myocardial infarction (AMI), high mobility group box-1 (HMGB1) injection has been demonstrated to be cardioprotective. Contrarily, some reports show that cardioprotection is achieved with HMGB1 inhibition. Given the lack of data in large mammals, we searched the dose that would promote angiogenesis and expression of cardiac specific regenerative genes in sheep with AMI (protocol 1) and subsequently, use this dose to study long-term effects on infarct size, microvessels density, cardiomyogenesis and echocardiographic left ventricular (LV) function (protocol 2). Methods and Results. Protocol 1: Sheep with AMI received 250 μg (high-dose, n=7), 25 μg (low-dose, n=7) HMGB1, or PBS (placebo, n=7) in 10 intramyocardial injections (0.2 ml each) in the peri-infarct area. Seven days later, as compared with placebo, only the high-HMGB1 dose group exhibited higher microvascular densities (2828±511 vs. 1711±194 capillaries/mm2, P