Recently, HMGB1 has been found to be passively released by necrotic cardiomyocytes in response to ischemia and it also acts as an early mediator of inflammation following I/R injury.5 Moreover, HMGB1 is also actively secreted by immune cells such as monocytes, macrophages and dendritic cells, which further enhances the inflammatory reaction. Here, HMGB1 is linked to ischemia.