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01.05.2012 | Article

Coenzyme Q₁₀ attenuates diastolic dysfunction, cardiomyocyte hypertrophy and cardiac fibrosis in the db/db mouse model of type 2 diabetes

verfasst von: K. Huynh, H. Kiriazis, X.-J. Du, J. E. Love, K. A. Jandeleit-Dahm, J. M. Forbes, J. R. McMullen, R. H. Ritchie

Erschienen in: Diabetologia | Ausgabe 5/2012

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Abstract

Aims/hypothesis

An increase in the production of reactive oxygen species is commonly thought to contribute to the development of diabetic cardiomyopathy. This study aimed to assess whether administration of the antioxidant coenzyme Q₁₀ would protect the diabetic heart against dysfunction and remodelling, using the db/db mouse model of type 2 diabetes. Furthermore, we aimed to compare the efficacy of coenzyme Q₁₀ to that of the ACE inhibitor ramipril.

Methods

Six-week-old non-diabetic db/+ mice and diabetic db/db mice received either normal drinking water or water supplemented with coenzyme Q₁₀ for 10 weeks. Endpoint cardiac function was assessed by echocardiography and catheterisation. Ventricular tissue was collected for histology, gene expression and protein analysis.

Results

Untreated db/db diabetic mice exhibited hyperglycaemia, accompanied by diastolic dysfunction and adverse structural remodelling, including cardiomyocyte hypertrophy, myocardial fibrosis and increased apoptosis. Systemic lipid peroxidation and myocardial superoxide generation were also elevated in db/db mice. Coenzyme Q₁₀ and ramipril treatment reduced superoxide generation, ameliorated diastolic dysfunction and reduced cardiomyocyte hypertrophy and fibrosis in db/db mice. Phosphorylation of Akt, although depressed in untreated db/db mice, was restored with coenzyme Q₁₀ administration. We postulate that preservation of cardioprotective Akt signalling may be a mechanism by which coenzyme Q₁₀-treated db/db mice are protected from pathological cardiac hypertrophy.

Conclusions/interpretation

These data demonstrate that coenzyme Q₁₀ attenuates oxidative stress and left ventricular diastolic dysfunction and remodelling in the diabetic heart. Addition of coenzyme Q₁₀ to the current therapy used in diabetic patients with diastolic dysfunction warrants further investigation.

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Titel: Coenzyme Q10 attenuates diastolic dysfunction, cardiomyocyte hypertrophy and cardiac fibrosis in the db/db mouse model of type 2 diabetes
verfasst von: K. Huynh
H. Kiriazis
X.-J. Du
J. E. Love
K. A. Jandeleit-Dahm
J. M. Forbes
J. R. McMullen
R. H. Ritchie
Publikationsdatum: 01.05.2012
Verlag: Springer-Verlag
Erschienen in: Diabetologia / Ausgabe 5/2012
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-012-2495-3

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Abstract

Aims/hypothesis

Methods

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Conclusions/interpretation

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