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Am J Physiol Heart Circ Physiol. 2011 Oct;301(4):H1220-8. doi: 10.1152/ajpheart.00601.2011. Epub 2011 Jul 22.

Desmin-related cardiomyopathy: an unfolding story.

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1
Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA.

Abstract

The intermediate filament protein desmin is an integral component of the cardiomyocyte and serves to maintain the overall structure and cytoskeletal organization within striated muscle cells. Desmin-related myopathy can be caused by mutations in desmin or associated proteins, which leads to intracellular accumulation of misfolded protein and production of soluble pre-amyloid oligomers, which leads to weakened skeletal and cardiac muscle. In this review, we examine the cellular phenotypes in relevant animal models of desmin-related cardiomyopathy. These models display characteristic sarcoplasmic protein aggregates. Aberrant protein aggregation leads to mitochondrial dysfunction, abnormal metabolism, and altered cardiomyocyte structure. These deficits to cardiomyocyte function may stem from impaired cellular proteolytic mechanisms. The data obtained from these models allow a more complete picture of the pathology in desmin-related cardiomyopathy to be described. Moreover, these studies highlight the importance of desmin in maintaining cardiomyocyte structure and illustrate how disrupting this network can be deleterious to the heart. We emphasize the similarities observed between desmin-related cardiomyopathy and other protein conformational disorders and speculate that therapies to treat this disease may be broadly applicable to diverse protein aggregation-based disorders.

PMID:
21784990
PMCID:
PMC3197348
DOI:
10.1152/ajpheart.00601.2011
[Indexed for MEDLINE]
Free PMC Article
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