Document Detail


Aldehydic load and aldehyde dehydrogenase 2 profile during the progression of post-myocardial infarction cardiomyopathy: Benefits of Alda-1.
MedLine Citation:
PMID:  25464432     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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, aldehydic load and mitochondrial bioenergetics during progression of post-myocardial infarction (post-MI) cardiomyopathy are unknown and should be established to determine the optimal time window for drug treatment.
METHODS: Here we characterized cardiac ALDH2 activity and expression, lipid peroxidation, 4-hydroxy-2-nonenal (4-HNE) adduct formation, glutathione pool and mitochondrial energy metabolism and H2O2 release during the 4weeks after permanent left anterior descending (LAD) coronary artery occlusion in rats.
RESULTS: We observed a sustained disruption of cardiac mitochondrial function during the progression of post-MI cardiomyopathy, characterized by >50% reduced mitochondrial respiratory control ratios and up to 2 fold increase in H2O2 release. Mitochondrial dysfunction was accompanied by accumulation of cardiac and circulating lipid peroxides and 4-HNE protein adducts and down-regulation of electron transport chain complexes I and V. Moreover, increased aldehydic load was associated with a 90% reduction in cardiac ALDH2 activity and increased glutathione pool. Further supporting an ALDH2 mechanism, sustained Alda-1 treatment (starting 24h after permanent LAD occlusion surgery) prevented aldehydic overload, mitochondrial dysfunction and improved ventricular function in post-MI cardiomyopathy rats.
CONCLUSION: Taken together, our findings demonstrate a disrupted mitochondrial metabolism along with an insufficient cardiac ALDH2-mediated aldehyde clearance during the progression of ventricular dysfunction, suggesting a potential therapeutic value of ALDH2 activators during the progression of post-myocardial infarction cardiomyopathy.
Authors:
Katia M S Gomes; Luiz R G Bechara; Vanessa M Lima; Márcio A C Ribeiro; Juliane C Campos; Paulo M Dourado; Alicia J Kowaltowski; Daria Mochly-Rosen; Julio C B Ferreira
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-10-23
Journal Detail:
Title:  International journal of cardiology     Volume:  179C     ISSN:  1874-1754     ISO Abbreviation:  Int. J. Cardiol.     Publication Date:  2014 Oct 
Date Detail:
Created Date:  2014-12-2     Completed Date:  -     Revised Date:  2014-12-3    
Medline Journal Info:
Nlm Unique ID:  8200291     Medline TA:  Int J Cardiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  129-138     Citation Subset:  -    
Copyright Information:
Copyright © 2014. Published by Elsevier Ireland Ltd.
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