Abstract 17455: Genetic Deficiency of the H2S Producing Enzyme 3-mercaptopyruvate sulfurtransferase (3-MST) Exacerbates Myocardia Ischemia/Reperfusion (MI/R) Injury
Background: Hydrogen Sulfide (H2S) protects against acute myocardial ischemia/reperfusion (MI/R) injury and heart failure by ameliorating oxidative stress, reducing apoptosis, and attenuating inflammation. 3-mercaptopyruvate sulfurtransferase (3-MST) is one of three known H2S producing enzymes in the body. It is primarily localized in the mitochondria. The purpose of this study was to investigate whether 3-MST production of H2S directly impacts myocardial ischemia reperfusion injury and mitochondrial function.
Methods: Global 3-MST KO and wild-type (WT) mice (n = 8-9 per group) between 10-12 weeks of age were subjected to 45 min of myocardial ischemia and 24 h of reperfusion. Blood was collected for troponin-I measurements at 24 hours post ischemia. Cardiac mitochondria were isolated by differential centrifugation and base line measurements were taken using an Oxygraph O2 electrode system (Hansatech, Norfolk, England).
Results: The 3-MST KO mice had significantly elevated cardiac troponin-I levels compared to the wild-type mice (118.5 vs. 44.98 ng/mL, p<0.05). In isolated mitochondria, the KO mice exhibited decreased State 3 respiration (1.274 μM vs. 0.9715 μM O2/sec/mg, p<0.05) and the Respiratory Control Ratio (RCR) levels were also declined in the mutant mouse (5.014 vs. 3.642, p<0.05).
Conclusion: Deficiency of 3-MST appears to have a significant impact on acute myocardial ischemia/reperfusion injury. The 3-MST KO mice also exhibit exacerbated mitochondrial respiration. These results suggest that endogenously produced H2S via 3-MST enzyme in the mitochondria plays a cytoprotective role in the setting of MI/R injury.
- Mitochondrial energetics, heart failure, arrhythmias
- Myocardial infarction
- Cardiac metabolism
- © 2013 by American Heart Association, Inc.