Oxidative stress causes heart failure with impaired mitochondrial respiration.
J Biol Chem
; 281(44): 33789-801, 2006 Nov 03.
Article
en En
| MEDLINE
| ID: mdl-16959785
Elderly people insidiously manifest the symptoms of heart failure, such as dyspnea and/or physical disabilities in an age-dependent manner. Although previous studies suggested that oxidative stress plays a pathological role in the development of heart failure, no direct evidence has been documented so far. In order to investigate the pathological significance of oxidative stress in the heart, we generated heart/muscle-specific manganese superoxide dismutase-deficient mice. The mutant mice developed progressive congestive heart failure with specific molecular defects in mitochondrial respiration. In this paper, we showed for the first time that the oxidative stress caused specific morphological changes of mitochondria, excess formation of superoxide (O(2)(*)(-)), reduction of ATP, and transcriptional alterations of genes associated with heart failure in respect to cardiac contractility. Accordingly, administration of a superoxide dismutase mimetic significantly ameliorated the symptoms. These results implied that O(2)(*)(-) generated in mitochondria played a pivotal role in the development and progression of heart failure. We here present a bona fide model for human cardiac failure with oxidative stress valuable for therapeutic interventions.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Estrés Oxidativo
/
Cardiopatías
/
Mitocondrias Cardíacas
Tipo de estudio:
Etiology_studies
Límite:
Animals
Idioma:
En
Revista:
J Biol Chem
Año:
2006
Tipo del documento:
Article
País de afiliación:
Japón
Pais de publicación:
Estados Unidos