Abstract 14115: Mitochondrial Targeted DNA Repair Enzyme 8-oxoguanene DNA Glycosylase 1 (OGG1) Attenuates Myocardial Infarct Size
Objective: Myocardial ischemia/reperfusion (MI/R) injury is mediated in part by increased oxidative stress and DNA damage. MI/R is one of the leading causes of increased patient morbidity and mortality in coronary artery bypass grafting (CABG) surgery. We hypothesized that enhanced mtDNA repair via mitochondrial targeted DNA repair with the mtDNA repair enzyme, 8-oxoguanine DNA glycosylase 1 (OGG1), would attenuate MI/R injury.
Methods and Results: Male C57BL/6J (10-12 weeks) was subjected to 45 min. of MI and 24 hr. of R. OGG1 (4 mg/kg) or vehicle (VEH) was administered 5 minutes before reperfusion. Serum troponin-I was measured at 4 hr. R and infarct size per area-at-risk (INF/AAR) was evaluated at 24 hours R. OGG1 reduced INF/AAR by 38.6% (p < 0.05 vs. VEH) and significantly reduced troponin-I levels (p < 0.01 vs. VEH). In contrast, mutant enzymatically inactive OGG1 failed to attenuate myocardial infarct size.
Conclusions: Our results indicate that OGG1 just prior to the time of reperfusion promotes myocardial salvage in the setting of MI/R.
- © 2013 by American Heart Association, Inc.