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

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art_GOMES_Aldehydic_load_and_aldehyde_dehydrogenase_2_profile_during_2015.PDF (1.78 MB)
Citações na Scopus
52
Tipo de produção
article
Data de publicação
2015
Editora
ELSEVIER IRELAND LTD
DOI
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Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Autores
GOMES, Katia M. S.
BECHARA, Luiz R. G.
LIMA, Vanessa M.
RIBEIRO, Marcio A. C.
CAMPOS, Juliane C.
KOWALTOWSKI, Alicia J.
MOCHLY-ROSEN, Daria
FERREIRA, Julio C. B.
Autor de Grupo de pesquisa
Editores
Coordenadores
Organizadores
Citação
INTERNATIONAL JOURNAL OF CARDIOLOGY, v.179, p.129-138, 2015
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
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 4 weeks 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 24 h 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.
Palavras-chave
Myocardial infarction, 4-Hydroxynonenal, Oxidative stress, Bioenergetics, Aldehyde dehydrogenase 2
URI
https://observatorio.fm.usp.br/handle/OPI/9156
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Coleções
Artigos e Materiais de Revistas Científicas - HC/InCor