Journal article
Transgenic overexpression of caveolin-3 in the heart induces a cardiomyopathic phenotype
Human molecular genetics, Vol.12(21), pp.2777-2788
2003
DOI: 10.1093/hmg/ddg313
PMID: 12966035
Abstract
Caveolins are structural protein components of caveolar membrane domains. Caveolin-3, a muscle-specific member of the caveolin family, is expressed in skeletal muscle tissue and in the heart. The multiple roles that caveolin-3 plays in cellular physiology are becoming more apparent. We have shown that lack of caveolin-3 expression in skeletal muscle resembles limb-girdle muscular dystrophy-1C. In contrast, we have demonstrated that overexpression of caveolin-3 in skeletal muscle tissue promotes defects similar to those seen in Duchenne muscular dystrophy (DMD). Thus, a tight regulation of caveolin-3 expression is fundamental for normal muscle functions. Since caveolin-3 is also endogenously expressed in cardiac myocytes, and cardiomyopathies are observed in DMD patients, we looked at the effects of overexpression of caveolin-3 on cardiac structure and function by characterizing caveolin-3 transgenic mice. Our results indicate that overexpression of caveolin-3 causes severe cardiac tissue degeneration, fibrosis and a reduction in cardiac functions. We also show that dystrophin and its associated glycoproteins are down-regulated in caveolin-3 transgenic heart. In addition, we demonstrate that the activity of nitric oxide synthase (NOS) is down-regulated by high levels of caveolin-3 in the heart. Taken together, these results indicate that overexpression of caveolin-3 is sufficient to induce severe cardiomyopathy. In addition, these findings suggest that caveolin-3 transgenic mice may represent a valid mouse model for studying the molecular mechanisms underlying cardiomyopathies associated with Duchenne muscular dystrophy.
Details
- Title: Subtitle
- Transgenic overexpression of caveolin-3 in the heart induces a cardiomyopathic phenotype
- Creators
- Bharathi ARAVAMUDAN - Department of Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, United StatesDaniela VOLONTE - Department of Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, United StatesRavi RAMANI - The Cardiovascular Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, United StatesErdal GURSOY - The Cardiovascular Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, United StatesMichael P LISANTI - Albert Einstein College of MedicineBarry LONDON - The Cardiovascular Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, United StatesFerruccio GALBIATI - Department of Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, United States
- Resource Type
- Journal article
- Publication Details
- Human molecular genetics, Vol.12(21), pp.2777-2788
- Publisher
- Oxford University Press; Oxford
- DOI
- 10.1093/hmg/ddg313
- PMID
- 12966035
- ISSN
- 0964-6906
- eISSN
- 1460-2083
- Language
- English
- Date published
- 2003
- Academic Unit
- Molecular Physiology and Biophysics; Cardiovascular Medicine; Internal Medicine
- Record Identifier
- 9984025671202771
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