BAG3 and diabetes mellitus: As shown in Figure 8, these results suggest that diabetes exacerbates myocardial IR-induced dysfunction and injury through the upregulation of NADPH oxidase p22- and p67-mediated oxidative stress and downregulation of Nrf-2/HO-1, BAG3 and Bcl-2 in the myocardium, leading to further cardiac dysfunction and cardiovascular injury.