Aldehydic load and aldehyde dehydrogenase 2 profile during the progression of post-myocardial infarction cardiomyopathy: Benefits of Alda-1☆

摘要: Abstract Background/objectives We previously demonstrated that reducing cardiac aldehydic load by aldehyde dehydrogenase 2 (ALDH2), a mitochondrial enzyme responsible for metabolizing the major lipid peroxidation product, protects against acute ischemia/reperfusion injury and chronic heart failure. However, time-dependent changes in ALDH2 profile, bioenergetics during progression of post-myocardial infarction (post-MI) cardiomyopathy are unknown should be established to determine optimal time window drug treatment. Methods Here we characterized activity expression, peroxidation, 4-hydroxy-2-nonenal (4-HNE) adduct formation, glutathione pool energy metabolism H O release 4weeks after permanent left anterior descending (LAD) coronary artery occlusion rats. Results observed sustained disruption function post-MI cardiomyopathy, >50% reduced respiratory control ratios up fold increase release. Mitochondrial dysfunction was accompanied accumulation circulating peroxides 4-HNE protein adducts down-regulation electron transport chain complexes I V. Moreover, increased associated with 90% reduction pool. Further supporting an mechanism, Alda-1 treatment (starting 24h LAD surgery) prevented overload, improved ventricular Conclusion Taken together, our findings demonstrate disrupted along insufficient ALDH2-mediated clearance dysfunction, suggesting potential therapeutic value activators cardiomyopathy.