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Master's Dissertation
DOI
https://doi.org/10.11606/D.42.2014.tde-12082014-201637
Document
Author
Full name
Katia Maria Sampaio Gomes
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2014
Supervisor
Committee
Ferreira, Julio Cesar Batista (President)
Miyabara, Elen Haruka
Oliveira, Edilamar Menezes de
Title in Portuguese
Participação da enzima aldeído desidrogenase 2 na insuficiência cardíaca induzida por infarto do miocárdio.
Keywords in Portuguese
4HNE
Alda-1
ALDH2
Estresse oxidativo
Insuficiência cardíaca
Abstract in Portuguese
A formação de aldeídos decorrente do estresse oxidativo é cardiotóxica e contribui para o aparecimento das doenças cardiovasculares. O aldeído 4-hidroxi-2-nonenal (4HNE) apresenta grande poder nocivo cardíaco. A enzima mitocondrial aldeído desidrogenase 2 (ALDH2) é a principal responsável pela remoção do 4HNE, sendo que a ativação farmacológica da ALDH2 previne danos cardíacos oriundos do processo de isquemia/reperfusão. Com o intuito de compreender o papel desta enzima na insuficiência cardíaca (IC) tivemos como objetivos: caracterizar o curso temporal de ativação da ALDH2 pós-infarto do miocárdio em ratos e estudar o efeito da ativação farmacológica sustentada da ALDH2 na IC. Nossos resultados apontam que na 1ª, 2ª e 4ª semanas pós-infarto a atividade da ALDH2 apresenta-se reduzida. Essa redução está associada à disfunção mitocondrial e cardíaca. Contudo, o tratamento com Alda-1 proporciona uma melhora dessas funções. Assim, concluímos que a ativação seletiva da ALDH2 reduz danos cardíacos, podendo ser considerada um novo alvo terapêutico no tratamento da IC.
Title in English
Role of aldehyde dehydrogenase 2 in myocardial infarction-induced heart failure.
Keywords in English
4HNE
Alda-1
ALDH2
Heart failure
Oxidative stress
Abstract in English
Here we determined the benefits of chronic activation of ALDH2 on the progression of heart failure after the onset of symptoms using a post-myocardial infarction model. We showed that a six-week treatment of myocardial infarction-induced heart failure rats with Alda-1, a selective ALDH2 activator, enhanced contractile function, improved left ventricular compliance and increased diastolic dysfunction under basal conditions and after sudden pressure-overload stress. Moreover, sustained Alda-1 treatment showed no toxicity and promoted a cardiac anti-remodeling effect by suppressing myocardial hypertrophy and fibrosis. Moreover, ALDH2 activation-mediated cardioprotection was associated with improved mitochondrial function. Further Alda-1 treatment preserved mitochondrial function in vitro upon 4-HNE addition. Therefore, selective activation of mitochondrial ALDH2 reduces aldehydic load, preserves mitochondrial function and improves heart failure outcome, suggesting that ALDH2 activators have a potential therapeutic value for treating heart failure patients.
 
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Publishing Date
2014-08-14
 
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