Aldehyde Dehydrogenase-2 Attenuates Myocardial Remodeling and Contractile Dysfunction Induced by a High-Fat Diet.
Cell Physiol Biochem
; 48(5): 1843-1853, 2018.
Article
em En
| MEDLINE
| ID: mdl-30092566
BACKGROUND/AIMS: Consumption of a high-fat (HF) diet exacerbates metabolic cardiomyopathy through lipotoxic mechanisms. In this study, we explored the role of aldehyde dehydrogenase-2 (ALDH2) in myocardial damage induced by a HF diet. METHODS: Wild-type C57 BL/6J mice were fed a HF diet or control diet for 16 weeks. ALDH2 overexpression was achieved by injecting a lentiviral ALDH2 expression vector into the left ventricle. RESULTS: Consumption of a HF diet induced metabolic syndrome and myocardial remodeling, and these deleterious effects were attenuated by ALDH2 overexpression. In addition, ALDH2 overexpression attenuated the cellular apoptosis and insulin resistance associated with a HF diet. Mechanistically, ALDH2 overexpression inhibited the expression of c-Jun N-terminal kinase (JNK)-1, activated protein 1 (AP-1), insulin receptor substrate 1 (IRS-1), 4- hydroxynonenal, caspase 3, transforming growth factor ß1, and collagen I and III, and enhanced Akt phosphorylation. CONCLUSION: ALDH2 may effectively attenuate myocardial remodeling and contractile defects induced by a HF diet through the regulation of the JNK/AP-1 and IRS-1/Akt signaling pathways. Our study demonstrates that ALDH2 plays an essential role in protecting cardiac function from lipotoxic cardiomyopathy.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Dieta Hiperlipídica
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Aldeído-Desidrogenase Mitocondrial
/
Miocárdio
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article