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J. Biol. Chem., Vol. 277, Issue 41, 38988-38997, October 11, 2002
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From the a Department of Molecular Pharmacology,
b Division of Hormone-Dependent Tumor Biology, Albert Einstein
College of Medicine, the f Divisions of Cardiology and
Infectious Disease, Department of Medicine, Albert Einstein College of
Medicine and Montefiore Medical Center, the h Department of
Physiology and Biophysics, Albert Einstein College of Medicine, the
i Departments of Urology, Physiology, and Biophysics, Institute
for Smooth Muscle Biology, Albert Einstein College of Medicine, and the
g Department of Pathology, Albert Einstein College of Medicine,
Bronx, New York 10461
A growing body of evidence suggests that muscle
cell caveolae may function as specialized membrane micro-domains in
which the dystrophin-glycoprotein complex and cellular signaling
molecules reside. Caveolin-3 (Cav-3) is the only caveolin family member expressed in striated muscle cell types (cardiac and skeletal). Interestingly, skeletal muscle fibers from Cav-3 (
Caveolin-3 Knock-out Mice Develop a Progressive Cardiomyopathy
and Show Hyperactivation of the p42/44 MAPK Cascade*
/) knock-out mice
show a number of myopathic changes, consistent with a mild-to-moderate muscular dystrophy phenotype. However, it remains unknown whether a
loss of Cav-3 affects the phenotypic behavior cardiac myocytes in
vivo. Here, we present a detailed characterization of the hearts of Cav-3 knock-out mice. We show that these mice develop a progressive cardiomyopathic phenotype. At four months of age, Cav-3 knock-out hearts display significant hypertrophy, dilation, and reduced fractional shortening, as revealed by gated cardiac MRI and
transthoracic echocardiography. Histological analysis reveals marked
cardiac myocyte hypertrophy, with accompanying cellular infiltrates and progressive interstitial/peri-vascular fibrosis. Interestingly, loss of
Cav-3 expression in the heart does not change the expression or the
membrane association of the dystrophin-glycoprotein (DG) complex.
However, a marker of the DG complex, 
-sarcoglycan, was specifically
excluded from lipid raft domains in the absence of Cav-3. Because
activation of the Ras-p42/44 MAPK pathway in cardiac myocytes
can drive cardiac hypertrophy, we next assessed the activation state of
this pathway using a phospho-specific antibody probe. We show that
p42/44 MAPK (ERK1/2) is hyperactivated in hearts derived from Cav-3
knock-out mice. These results are consistent with previous in
vitro data demonstrating that caveolins may function as negative
regulators of the p42/44 MAPK cascade. Taken together, our data argue
that loss of Cav-3 expression is sufficient to induce a molecular
program leading to cardiac myocyte hypertrophy and cardiomyopathy.
*
This work was supported in part by grants from the National
Institutes of Health (NIH), the Muscular Dystrophy Association, and the
American Heart Association (all to M. P. L.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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|
|
|
|
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|
|
|
 |
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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