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.