| Interplay between heart and skeletal muscle disease in heart failure: the 2011 George E. Brown Memorial Lecture. | |
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MedLine Citation:
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PMID: 22383709 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The study of single gene disorders often provides insight for more complex human disease. Mutations in the genes encoding the dystrophin protein complex cause muscular dystrophy and cardiomyopathy by destabilizing the plasma membrane of skeletal myofibers and cardiomyocytes. In these diseases, progressive skeletal muscle degeneration and weakness contribute to cardiac dysfunction. Moreover, the pace and pattern of muscle weakness, along with onset of cardiomyopathy, is highly variable even when associated with the same identical mutation. Using a mouse model of muscular dystrophy and cardiomyopathy, we identified genetic loci that modify muscle pathology and cardiac fibrosis. Distinct genetic modifiers were identified for diaphragm and abdominal musculature, and these genetic intervals differ from those that regulate pathology in the skeletal muscle of the limbs and the heart. One modifier gene was identified and highlights the importance of the transforming growth factor-β pathway in the pathogenesis of muscular dystrophy and cardiomyopathy. We determined that canonical transforming growth factor-β signaling contributes to heart and muscle dysfunction using a Drosophila model. Together, these studies demonstrate the value of using a genetically sensitized model to uncover pathways that regulate heart failure and muscle weakness. |
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Authors:
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Elizabeth M McNally; Jeffery A Goldstein |
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Publication Detail:
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Type: Lectures; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Circulation research Volume: 110 ISSN: 1524-4571 ISO Abbreviation: Circ. Res. Publication Date: 2012 Mar |
Date Detail:
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Created Date: 2012-03-02 Completed Date: 2012-05-03 Revised Date: 2013-04-15 |
Medline Journal Info:
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Nlm Unique ID: 0047103 Medline TA: Circ Res Country: United States |
Other Details:
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Languages: eng Pagination: 749-54 Citation Subset: IM |
Affiliation:
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Department of Medicine, University of Chicago, Chicago, IL 60637, USA. emcnally@uchicago.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cardiomyopathies / physiopathology Disease Models, Animal Drosophila Heart / physiopathology* Heart Failure / physiopathology* Mice Muscle, Skeletal / physiopathology* Muscular Dystrophies / physiopathology Signal Transduction / physiology Transforming Growth Factor beta / physiology |
| Grant Support | |
ID/Acronym/Agency:
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P01 NS072027-01A1/NS/NINDS NIH HHS; R01 AR050703-02/AR/NIAMS NIH HHS; R01 HL061322-10S1/HL/NHLBI NIH HHS; R01 HL061322-11/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Transforming Growth Factor beta |
| Comments/Corrections | |
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