Angiotensin 1-7 ameliorates diabetic cardiomyopathy and diastolic dysfunction in db/db mice by reducing lipotoxicity and inflammation.
Circ Heart Fail
; 7(2): 327-39, 2014 Mar 01.
Article
em En
| MEDLINE
| ID: mdl-24389129
ABSTRACT
BACKGROUND:
The angiotensin-converting enzyme 2 and angiotensin-(1-7) (Ang 1-7)/MasR (Mas receptor) axis are emerging as a key pathway that can modulate the development of diabetic cardiomyopathy. We studied the effects of Ang 1-7 on diabetic cardiomyopathy in db/db diabetic mice to elucidate the therapeutic effects and mechanism of action. METHODS ANDRESULTS:
Ang 1-7 was administered to 5-month-old male db/db mice for 28 days via implanted micro-osmotic pumps. Ang 1-7 treatment ameliorated myocardial hypertrophy and fibrosis with normalization of diastolic dysfunction assessed by pressure-volume loop analysis and echocardiography. The functional improvement by Ang 1-7 was accompanied by a reduction in myocardial lipid accumulation and systemic fat mass and inflammation and increased insulin-stimulated myocardial glucose oxidation. Increased myocardial protein kinase C levels and loss of phosphorylation of extracellular signal-regulated kinase 1/2 were prevented by Ang 1-7. Furthermore, Ang 1-7 treatment decreased cardiac triacylglycerol and ceramide levels in db/db mice, concomitantly with an increase in myocardial adipose triglyceride lipase expression. Changes in adipose triglyceride lipase expression correlated with increased SIRT1 (silent mating type information regulation 2 homolog 1) levels and deacetylation of FOXO1 (forkhead box O1).CONCLUSIONS:
We identified a novel beneficial effect of Ang 1-7 on diabetic cardiomyopathy that involved a reduction in cardiac hypertrophy and lipotoxicity, adipose inflammation, and an upregulation of adipose triglyceride lipase. Ang 1-7 completely rescued the diastolic dysfunction in the db/db model. Ang 1-7 represents a promising therapy for diabetic cardiomyopathy associated with type 2 diabetes mellitus.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Fragmentos de Peptídeos
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Angiotensina I
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Função Ventricular
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Disfunção Ventricular Esquerda
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Diabetes Mellitus Experimental
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Cardiomiopatias Diabéticas
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Inflamação
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Lipídeos
Tipo de estudo:
Diagnostic_studies
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Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article