Improvement of cardiac fibrosis in dystrophic mice by rAAV9-mediated microdystrophin transduction
| Autor: | Shin Jh, Takashi Okada, Shin'ichi Takeda, Yuko Nitahara-Kasahara, Hironori Okada, Hiromi Hayashita-Kinoh, Tomoko Chiyo, Kinoshita K, Ohshima-Hosoyama S |
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| Rok vydání: | 2011 |
| Předmět: |
medicine.medical_specialty
Aging Cardiac fibrosis Genetic enhancement Duchenne muscular dystrophy Genetic Vectors Cardiomyopathy Gene delivery Dystrophin Mice Fibrosis Transduction Genetic Internal medicine Genetics Medicine Animals Humans Transgenes Molecular Biology Cause of death medicine.diagnostic_test business.industry Myocardium Genetic Therapy Dependovirus medicine.disease Virology Muscular Dystrophy Duchenne cardiovascular system Cardiology Mice Inbred mdx Molecular Medicine business Cardiomyopathies Electrocardiography |
| Zdroj: | Gene therapy. 18(9) |
| ISSN: | 1476-5462 |
| Popis: | Duchenne muscular dystrophy (DMD) is the most common form of the progressive muscular dystrophies characterized by defects of the dystrophin gene. Although primarily characterized by degeneration of the limb muscles, cardiomyopathy is a major cause of death. Therefore, the development of curative modalities such as gene therapy is imperative. We evaluated the cardiomyopathic features of mdx mice to observe improvements in response to intravenous administration of recombinant adeno-associated virus (AAV) type 9 encoding microdystrophin. The myocardium was extensively transduced with microdystrophin to significantly prevent the development of fibrosis, and expression persisted for the duration of the study. Intraventricular conduction patterns, such as the QRS complex duration and S/R ratio in electrocardiography, were also corrected, indicating that the transduced microdystrophin has a protective effect on the dystrophin-deficient myocardium. Furthermore, BNP and ANP levels were reduced to normal, suggesting the absence of cardiac dysfunction. In aged mice, prevention of ectopic beats as well as echocardiographic amelioration was also demonstrated with improved exercise performance. These findings indicate that AAV-mediated cardiac transduction with microdystrophin might be a promising therapeutic strategy for the treatment of dystrophin-deficient cardiomyopathy. |
| Databáze: | OpenAIRE |
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