| Systemic administration of micro-dystrophin restores cardiac geometry and prevents dobutamine-induced cardiac pump failure. | |
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MedLine Citation:
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PMID: 17440445 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Duchenne muscular dystrophy (DMD) is a fatal disease of striated muscle deterioration resulting from the loss of the cytoskeletal protein dystrophin. Most patients develop significant cardiomyopathy, with heart failure being the second leading cause of death in DMD. Compared with the extensive studies on skeletal muscle defects and potential therapy in DMD, very little attention has been directed at the increasing incidence of heart failure in DMD. Here we show that a single systemic injection of recombinant adeno-associated virus (rAAV2/6) harboring micro-dystrophin leads to extensive cardiac transduction, with micro-dystrophin correctly localized at the periphery of the cardiac myocytes and functionally associated with the sarcolemmal membrane. Significantly, micro-dystrophin gene transfer corrected the baseline end-diastolic volume defect in the mdx mouse heart and prevented cardiac pump failure induced by dobutamine stress testing in vivo, although several parameters of systolic function were not corrected. These results demonstrate that systemic gene delivery of micro-dystrophin can restore ventricular distensibility and protect the mdx myocardium from pump dysfunction during adrenergic stimulation in vivo. |
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Authors:
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DeWayne Townsend; Michael J Blankinship; James M Allen; Paul Gregorevic; Jeffrey S Chamberlain; Joseph M Metzger |
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Publication Detail:
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Type: Journal Article Date: 2007-04-17 |
Journal Detail:
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Title: Molecular therapy : the journal of the American Society of Gene Therapy Volume: 15 ISSN: 1525-0016 ISO Abbreviation: Mol. Ther. Publication Date: 2007 Jun |
Date Detail:
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Created Date: 2007-05-18 Completed Date: 2007-09-25 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100890581 Medline TA: Mol Ther Country: United States |
Other Details:
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Languages: eng Pagination: 1086-92 Citation Subset: IM |
Affiliation:
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Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan, USA. dtown@umich.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adrenergic beta-Agonists
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toxicity Animals Blotting, Western Cardiomyopathies / chemically induced, therapy* Dependovirus / genetics* Dobutamine / toxicity Dystrophin / genetics*, metabolism Fluorescent Antibody Technique Gene Therapy / methods* Genetic Vectors / administration & dosage, genetics Glycoproteins / metabolism Mice Mice, Inbred C57BL Mice, Inbred mdx Muscular Dystrophy, Duchenne / chemically induced, therapy* Myocardium / metabolism, pathology |
| Chemical | |
Reg. No./Substance:
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0/Adrenergic beta-Agonists; 0/Dystrophin; 0/Glycoproteins; 34368-04-2/Dobutamine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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