doi: 10.1161/CIRCULATIONAHA.107.189727
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(Circulation. 2008;117:2425-2427.)
© 2008 American Heart Association, Inc.
Clinical Summaries
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
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Selective Vacuolar Degeneration in Dystrophin-Deficient Canine Purkinje Fibers Despite Preservation of Dystrophin-Associated Proteins With Overexpression of Dp71 |
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In Duchenne muscular dystrophy, a devastating skeletal and cardiac muscle disorder caused by mutations in the dystrophin gene, cardiac failure such as dilated cardiomyopathy and arrhythmia needs to be overcome, although the respiratory management has significantly improved the life span of the patients. Among cardiac involvements, ECG findings such as distinctive deep Q waves have been noted and are ascribed to fibrosis in the posterobasal region of the left ventricle. When Urasawa et al (National Institute of Neuroscience, Tokyo, Japan) examined the hearts of dogs with canine X-linked muscular dystrophy in Japan (CXMDJ), an appropriate dystrophin-deficient model of Duchenne muscular dystrophy, the Purkinje fibers showed remarkable vacuolar degeneration as early as 4 months of age despite no detectable fibrotic lesions in ventricular myocardium. The degeneration of CXMDJ Purkinje fibers was coincident with overexpression of Dp71, a C-terminal truncated form of dystrophin, at the sarcolemma and translocation of calcium-dependent protease µ-calpain to the cell periphery near the sarcolemma or in the vacuoles. Utrophin, a homologue of dystrophin, was highly upregulated in the earlier stage of CXMDJ Purkinje fibers, but the expression was dislocated when vacuolar degeneration was recognized at 4 months of age, despite preservation of dystrophin-associated proteins at the sarcolemma. The selective degeneration of Purkinje fibers can be associated with distinct deep Q waves on ECG and the fatal arrhythmia seen in dystrophin deficiency. Further clarification of the molecular mechanism of selective degeneration of Purkinje fibers may shed light on the development of new therapy for cardiac involvement in
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