Background: Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) is involved in DNA base excision repair. It also controls the intracellular reactive oxygen species (ROS) production and has anti-inflammatory function against the vascular endothelial activation. To investigate the relationship between APE/Ref-1 and cardiac cell death with apoptosis, we examined the expression of APE/Ref-1 in a mouse model of myocardial infarction (MI).
Methods : Mouse (C57bl/6J) MI models were created by ligation of the left anterior descending coronary artery. Expression of the APE/Ref-1 protein was evaluated by Western blot. Immunohistochemistry was used for analysis of apoptosis and ROS generation.
Results: APE/Ref-1 was significantly increased after MI at one week (4 folds compared to control, p<0.01) sustained until 4 weeks. To confirm the beneficial role of APE/Ref-1 we made MI and randomly injected adeno-APE/Ref-1 virus or null virus into the myocardium. APE/Ref-1 injection group revealed decreased myocardial infacrtion size compared to control group (22.7% vs 45.8%, p<0.01) at 4weeks later. Immunohistochemistry showed that decreased ROS generation and decreased apoptosis in the APE/Ref-1 injection group 1 week after MI.
Conclusions: APE1/Ref-1 was significantly increased in a mouse MI model. Injecting APE1/Ref-1 decreased myocardial infacrtion size, ROS generation and apoptosis. These novel findings suggest that APE1/Ref-1 may be possible as a biomarker and has therapeutic potential for myocardial infacrtion.