Abstract 16615: Oxidative Modification of the Proteins Related to ATP Synthesis Leads to the Left Ventricular Dysfunction
Background: Under a hypothesis that inflammation enhanced by reactive oxygen species (ROS) accumulation plays an essential role in the progression of cardiovascular diseases, we investigated ROS-induced carbonyl modification of myocardial proteins involved in the cardiac dysfunction, using proteomics analysis.
Methods and Results: Using the two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) and 2D-oxyblot analysis combined with MALDI-TOF/TOF tandem mass spectrometry, we compared the changes in expression and modification of proteins in the whole left ventricle (LV) between control hamsters, dilated cardiomyopathy hamsters (TO-2), and hypertrophy cardiomyopathy hamsters (Bio14.6) at 6 weeks of age (n =6, each group). At 6 weeks of age, there were no significant differences in the heart weight and left ventricular function monitored by echocardiography among three strains. However, plasma cardiac troponin T concentration is significantly increased in TO-2 (p < 0.05) compared with control hamsters at 6 weeks of age. 2D Oxyblot analysis detected 18 proteins with increased carbonyl level in cardiomyopahty hamsters compared with the control hamsters. We found that the carbonyl modification of succinyl-CoA:3-ketoacid-coenzyme A transferase 1 was markedly increased in both TO-2 and Bio 14.6. In addition, the carbonylated levels of citrate synthase, dihydrolipoyl dehydrogenase, and ATP synthase subunit alpha were significantly increased in both two cardiomyopahty hamsters.
Conclusion: Oxidative damage to the proteins related ATP synthesis, including mitochondrial electron transport system and oxidative phosphorylation, in the myocardium may lead to the left ventricular dysfunction, which contribute to pathogenesis of cardiomyopathy.
- © 2011 by American Heart Association, Inc.