Transcriptional deficits in oxidative phosphorylation with statin myopathy.

Abstract:

INTRODUCTION:Hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, or statins, are widely used drugs for hyperlipidemia and are generally well-tolerated, but the can produce skeletal muscle toxicity. The molecular mechanisms driving statin myopathy are unknown. We investigated the effects of statin treatment and eccentric (damaging) exercise on transcriptional patterns between statin myopathy (Sym; N = 9) and statin-tolerant subjects (Asym; N = 6). METHODS:Skeletal muscle biopsies were collected 6 h post-exercise at baseline and after statin treatment. Subjects performed concentric (non-damaging) exercise with one leg and concentric + eccentric exercise with the other leg using a cross-over design between time-points. RESULTS:Sym as compared with Asym demonstrated decreased skeletal muscle gene expression for oxidative phosphorylation-related and mitochondrial ribosomal protein genes before and after statin treatment with eccentric exercise. CONCLUSIONS:These results suggest that pre-existing deficiencies in energy production may contribute to the development of symptoms during statin therapy, especially when muscle is exposed to eccentric exercise.

journal_name

Muscle Nerve

journal_title

Muscle & nerve

authors

Hubal MJ,Reich KA,De Biase A,Bilbie C,Clarkson PM,Hoffman EP,Thompson PD

doi

10.1002/mus.22081

subject

Has Abstract

pub_date

2011-09-01 00:00:00

pages

393-401

issue

3

eissn

0148-639X

issn

1097-4598

journal_volume

44

pub_type

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