Disruption of caveolin-1 leads to enhanced nitrosative stress and severe systolic and diastolic heart failure.
Biochem Biophys Res Commun
; 340(2): 702-8, 2006 Feb 10.
Article
em En
| MEDLINE
| ID: mdl-16380094
ABSTRACT
Although caveolin-1 is not expressed in cardiomyocytes, this protein is assumed to act as a key regulator in the development of cardiomyopathy. In view of recent discordant findings we aimed to elucidate the cardiac phenotype of independently generated caveolin-1 knockout mice (cav-1(-/-)) and to unveil causative mechanisms. Invasive hemodynamic measurements of cav-1(-/-) show a severely reduced systolic and diastolic heart function. Additionally, genetic ablation of caveolin-1 leads to a striking biventricular hypertrophy and to a sustained eNOS-hyperactivation yielding increased systemic NO levels. Furthermore, a diminished ATP content and reduced levels of cyclic AMP in hearts of knockout animals were measured. Taken together, these results indicate that genetic disruption of caveolin-1 is sufficient to induce a severe biventricular hypertrophy with signs of systolic and diastolic heart failure. Collectively, our findings suggest a causative role of a sustained nitrosative stress in the development of the pronounced cardiac impairment.
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Coleções:
01-internacional
Contexto em Saúde:
6_ODS3_enfermedades_notrasmisibles
Base de dados:
MEDLINE
Assunto principal:
Cardiomiopatia Hipertrófica
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Óxido Nítrico Sintase Tipo III
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Caveolina 1
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Insuficiência Cardíaca
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Miocárdio
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Óxido Nítrico
Limite:
Animals
Idioma:
En
Revista:
Biochem Biophys Res Commun
Ano de publicação:
2006
Tipo de documento:
Article