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Statin-Induced Muscle Breakdown Linked to Gene

Atrogin-1 gene may be a critical mediator of muscle damage

MONDAY, Dec. 3 (HealthDay News) -- Lovastatin-induced muscle fiber breakdown, a side effect of therapy, is associated with induction of the atrogin-1 gene that may be a critical mediator of damage, according to a study in the December issue of the Journal of Clinical Investigation.

Jun-ichi Hanai, M.D., Ph.D., from Beth Israel Deaconess Medical Center in Boston, and colleagues investigated how lovastatin affected muscle in zebrafish embryos, cultured mouse skeletal muscle cells, and in humans with statin myopathy.

The researchers found that lovastatin induced the expression of atrogin-1, a gene involved in skeletal muscle atrophy. Lovastatin also promoted muscle fiber damage, while knockout of the atrogin-1 gene blocked lovastatin-induced muscle damage. Atrogin-1 induction was associated with morphological changes in cultured mouse myotubes. The investigators also found that overexpressing a transcriptional coactivator that protected against muscle atrophy blocked atrogin-1 induction.

"Collectively, our human, animal and in vitro findings shed light on the molecular mechanism of statin-induced myopathy and suggest that atrogin-1 may be a critical mediator of the muscle damage induced by statins," Hanai and colleagues conclude.

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