Abstract 14149: Mitochondrial Targeted DNA Repair Enzyme, Endonuclease III (ENDO III), Attenuates Myocardial Ischemia/Reperfusion Injury
Background: Previous studies have demonstrated that oxidative stress, mitochondrial dysfunction, and mitochondrial DNA (mtDNA) abnormalities contribute to cell death. Mitochondrial targeted DNA repair enzymes play a pivotal role in repairing oxidative damage to mtDNA. We hypothesized that mtDNA damage during myocardial ischemia/reperfusion (MI/R) injury could be attenuated by enhancing mtDNA repair via mitochondrial targeted DNA repair with the Endo III repair enzyme.
Methods: Male C57/BL6J (10-12 weeks) were subjected to 45 min. of MI and 24 hr. of R in vivo. Endo III (4 mg/kg) or vehicle (VEH) was administered 5 min. before R. Serum troponin-I was measured and infarct size per area-at-risk (INF/AAR) was evaluated at 24 hr. R. Two-dimensional echocardiography was performed at baseline, 1, 2, and 4 weeks post MI to assess left ventricular (LV) dimensions and ejection fraction (EF%).
Results: Endo III reduced INF/AAR by 50% (p < 0.01 vs. VEH) and significantly reduced troponin-I levels (p < 0.01 vs. VEH). Endo III significantly preserved LVEF (62.4 ± 7.2% vs. 42.9 ± 9.1%, p < 0.001) and improved left ventricular LV dimensions (LVEDD/LVESD; 3.48/2.35 mm vs. 4.04/3.24 mm, p < 0.001) at 4 weeks as compared to VEH.
Conclusions: These results demonstrate that Endo III administration at the time of reperfusion attenuates myocardial cell death and preserves cardiac function after MI/R. Studies are currently underway to define the cellular and molecular mechanisms by which Endo III protects the myocardium.
- © 2013 by American Heart Association, Inc.