Skip Navigation


Human Molecular Genetics Advance Access originally published online on September 9, 2003
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow A corrigendum has been published
Right arrow All Versions of this Article:
12/21/2777    most recent
ddg313v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (27)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Aravamudan, B.
Right arrow Articles by Galbiati, F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Aravamudan, B.
Right arrow Articles by Galbiati, F.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Human Molecular Genetics, 2003, Vol. 12, No. 21 2777-2788
DOI: 10.1093/hmg/ddg313
© 2003 Oxford University Press

Transgenic overexpression of caveolin-3 in the heart induces a cardiomyopathic phenotype

Bharathi Aravamudan1, Daniela Volonte1, Ravi Ramani2, Erdal Gursoy2, Michael P. Lisanti, Barry London2 and Ferruccio Galbiati1,*

1Department of Pharmacology and 2The Cardiovascular Institute, University of Pittsburgh School of Medicine,Pittsburgh, PA 15261, USA

Received June 14, 2003; Revised August 22, 2003; Accepted September 1, 2003

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.

* To whom correspondence should be addressed. Tel: +1 4126482047; Fax: +1 4126481945; E-mail: feg5{at}pitt.edu


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 DMMHome page
D. Merrick, L. K. J. Stadler, D. Larner, and J. Smith
Muscular dystrophy begins early in embryonic development deriving from stem cell loss and disrupted skeletal muscle formation
Dis. Model. Mech., July 1, 2009; 2(7-8): 374 - 388.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
Y. M. Tsutsumi, Y. T. Horikawa, M. M. Jennings, M. W. Kidd, I. R. Niesman, U. Yokoyama, B. P. Head, Y. Hagiwara, Y. Ishikawa, A. Miyanohara, et al.
Cardiac-Specific Overexpression of Caveolin-3 Induces Endogenous Cardiac Protection by Mimicking Ischemic Preconditioning
Circulation, November 4, 2008; 118(19): 1979 - 1988.
[Abstract] [Full Text] [PDF]

Home page
 HypertensionHome page
M. F. Dias-Peixoto, R. A.S. Santos, E. R.M. Gomes, M. N.M. Alves, P. W.M. Almeida, L. Greco, M. Rosa, B. Fauler, M. Bader, N. Alenina, et al.
Molecular Mechanisms Involved in the Angiotensin-(1-7)/Mas Signaling Pathway in Cardiomyocytes
Hypertension, September 1, 2008; 52(3): 542 - 548.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
D. Volonte, C. F. McTiernan, M. Drab, M. Kasper, and F. Galbiati
Caveolin-1 and caveolin-3 form heterooligomeric complexes in atrial cardiac myocytes that are required for doxorubicin-induced apoptosis
Am J Physiol Heart Circ Physiol, January 1, 2008; 294(1): H392 - H401.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
H. Abriel
Roles and regulation of the cardiac sodium channel Nav1.5: Recent insights from experimental studies
Cardiovasc Res, December 1, 2007; 76(3): 381 - 389.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
O. Feron and J.-L. Balligand
Caveolins and the regulation of endothelial nitric oxide synthase in the heart
Cardiovasc Res, March 1, 2006; 69(4): 788 - 797.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
A. Maguy, T. E. Hebert, and S. Nattel
Involvement of lipid rafts and caveolae in cardiac ion channel function
Cardiovasc Res, March 1, 2006; 69(4): 798 - 807.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. Rev.Home page
J. M. Nerbonne and R. S. Kass
Molecular Physiology of Cardiac Repolarization
Physiol Rev, October 1, 2005; 85(4): 1205 - 1253.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
S. J. Nixon, J. Wegner, C. Ferguson, P.-F. Mery, J. F. Hancock, P. D. Currie, B. Key, M. Westerfield, and R. G. Parton
Zebrafish as a model for caveolin-associated muscle disease; caveolin-3 is required for myofibril organization and muscle cell patterning
Hum. Mol. Genet., July 1, 2005; 14(13): 1727 - 1743.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
S. E Hardt and J. Sadoshima
Negative regulators of cardiac hypertrophy
Cardiovasc Res, August 15, 2004; 63(3): 500 - 509.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
J.-P. Gratton, P. Bernatchez, and W. C. Sessa
Caveolae and Caveolins in the Cardiovascular System
Circ. Res., June 11, 2004; 94(11): 1408 - 1417.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.