High doses of high mobility group box-1 (HMGB1) protein increase capillary and arteriolar densities and induce overexpression of genes involved in angiogenesis and cell proliferation in ovine infarct border zone

OLEA FD; BAUZÁ MR; LOCATELLI P; GIMÉNEZ CS; HNATIUK A; SGANGA L; CUNIBERTI L; CROTTOGINI A

Buenos Aires

Congreso; ISHR XXII Word Congress; 2016

International Society for Heart research

Introduction: In mice with AMI, administration of the pro-inflammatory protein HMGB-1 improved heart function and induced angiogenesis due to VEGF overexpression. CKit+ cells were also detected, suggesting cardiomyogenesis. However, neither the effects nor the optimal dose of HMGB-1 in large mammalian models of AMI have been addressed, this being important to develop translational therapies for humans. We thus assessed the effect of two doses of HMGB-1 on microvascular neoformation and the expression of genes involved in angiogenesis and cell proliferation in the infarct border zone of sheep with AMI.Methods: Twenty-one sheep with AMI received, 4 hours after coronary ligation, a total of 10 µg (high dose, n=7) or 1 µg (low dose, n=7) of HMGB1 in 10 intramyocardial injections in the peri-infarct zone. Placebo animals (n=7) received PBS. One week later, animals were sacrificed to quantify capillary and arteriolar densities (anti- lectin and smooth muscle actin immunohistochemistry, respectively) and expression of vegf, ckit, gata 4 and nkx2.5 genes (RT-qPCR).Results: Arteriolar density was higher than placebo in the high-dose group (39.4±11 vs. 23.2±4 arterioles/mm2, p