Cardiomyopathy in animal models of muscular dystrophy.

Abstract

Arrhythmia and cardiomyopathy frequently accompany muscular dystrophy. In the last year, the cardiovascular consequences of muscular dystrophy gene mutations have been established through studies of murine models. These models have highlighted the potential role of primary defects in cardiac muscle as well as those secondary cardiovascular outcomes that arise from severe muscle disease. This review focuses on three areas. Recent studies using mouse models have shown that the dystrophin-associated proteins, the sarcoglycans and alpha-dystrobrevin, are critical for both cardiac and skeletal muscle membrane function, yet may exert their roles by different molecular mechanisms. New findings have shown that cytoskeletal proteins at the nuclear membrane, such as emerin and lamin AC, cause muscular dystrophy and cardiomyopathy with cardiac conduction system disease. Finally, the mechanism of cardiac and muscle degeneration in myotonic dystrophy has been re-evaluated through a series of studies using murine models. Implications for human therapy are considered in light of these new findings.