SUMO2 deficiency impairs endogenous regulation of oxidative stress and apoptosis in myocardial ischemia-reperfusion injury.

Introduction: Myocardial ischemia-reperfusion injury (MIRI) is a major obstacle in the treatment of myocardial infarction and is closely associated with oxidative stress and cardiomyocyte death. Although endogenous protective mechanisms are activated during ischemic stress, they are often insufficient to prevent injury. SUMOylation is an important post-translational modification involved in cellular stress adaptation, and SUMO2 may contribute to the endogenous cardioprotective response. Methods: To investigate the role of SUMO2 in MIRI, we generated heart-specific SUMO2 knockout (SUMO2-KO) mice by crossing SUMO2-loxP mice with Myh6-Cre mice and assessed cardiac injury after myocardial infarction. In parallel, adeno-associated virus-mediated SUMO2 overexpression was used to assess the protective effect of SUMO2. In H9c2 cells subjected to oxygen-glucose deprivation, SUMO2 silencing was performed to examine reactive oxygen species (ROS) production, Bax/Bcl-2 balance, apoptosis, and p53-associated signaling. Results: SUMO2-KO mice exhibited more severe myocardial injury and worse cardiac dysfunction after ischemic injury. In contrast, SUMO2 overexpression markedly attenuated cardiac damage. In H9c2 cells, SUMO2 silencing increased ROS production, disrupted the Bax/Bcl-2 balance, and enhanced apoptosis. These effects were accompanied by alterations in p53-associated signaling. Discussion: These findings suggest that SUMO2 is an important regulator of endogenous cardioprotection during MIRI and may represent a potential target for future investigation.