Delivery of exogenous high mobility group box 1 (
HMGB1) may exert a beneficial effect on
myocardial ischemia-reperfusion (I/R) injury. Since the expression of
vascular endothelial growth factor (
VEGF) and
phosphatidylinositol 3-kinase/
protein kinase B (PI3K/Akt) in the myocardium mediates the cardioprotective function of
basic fibroblast growth factor, we hypothesized that
VEGF and the PI3K/Akt signaling pathway also mediate the protective effects of intravenously delivered
HMGB1. Thus, the objective of the present study was to analyze the impact of
intravenous administration of
HMGB1 on the myocardial expression of
VEGF, myocardial
fibrosis, and cardiac function in rats subjected to acute myocardial I/R. The
ischemia was induced by
ligation of the left anterior descending coronary artery for 30 min and was followed by 3 h of reperfusion. Myocardial
malondialdehyde content,
infarct size, and
collagen volume fraction decreased, while the activity of
superoxide dismutase was increased, the expression of
VEGF and p-Akt was upregulated, and cardiac function was improved in the HMGB1-treated group when compared with rats subjected to I/R only (all P < 0.05). However, these effects of
HMGB1 were abolished by
LY294002. The obtained results demonstrate that the cardioprotective effects of
intravenous administration of
HMGB1 prior to I/R may be mediated by upregulation of myocardial expression of
VEGF, which may activate the PI3K/Akt signaling pathway.