High-dose intramyocardial HMGB1 induces long-term cardioprotection in sheep with myocardial infarction

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

Drug Delivery and Translational Research

Springer

Lugar: Berlín; Año: 2019

2190-393X

In rodents with acute myocardial infarction (AMI), high mobility group box 1 (HMGB1) injection has produced controversial results. Given the lack of data in large mammals, we searched the dose that would promote angiogenesis and expression of specific regenerative genes in sheep with AMI (protocol 1) and, subsequently, use this dose to study long-term effects on infarct size and left ventricular (LV) function (protocol 2). 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, only the high-HMGB1-dose group exhibited higher microvascular densities, Ki67-positive cardiomyocytes, and overexpression of VEGF, Ckit, Tbx20, Nkx2.5, and Gata4. Protocol 2: Sheep with AMI received HMGB1 250 μg (n = 6) or PBS (n = 6). At 60 days, HMGB1-treated sheep showed smaller infarcts (8.5 ± 2.11 vs. 12.2 ± 1.97% LV area, P