How statins cause muscle damage

This study was published in the Journal of Clinical Investigation 2007 Dec;117(12):3940-51

Study title and authors:
The muscle-specific ubiquitin ligase atrogin-1/MAFbx mediates statin-induced muscle toxicity.

Hanai J, Cao P, Tanksale P, Imamura S, Koshimizu E, Zhao J, Kishi S, Yamashita M, Phillips PS, Sukhatme VP, Lecker SH.
Renal Division, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA.

This study can be accessed at: http://www.ncbi.nlm.nih.gov/pubmed/17992259

In 2001, scientists from the Harvard Medical School discovered the atrogin-1 gene, which plays a major role in muscle atrophy. (Muscle atrophy is the wasting or loss of muscle tissue).

Hanai notes that statins can lead to a number of side effects in muscle, including muscle fibre breakdown. This study sought to find the mechanisms of how statins may induce muscle injury. Since atrogin-1 plays a key role in the development of wasting in skeletal muscle, the study investigated if statins might “turn on” this gene.

They study comprised of three separate experiments to test this hypothesis.

(i) The first experiment examined the expression of the atrogin-1 gene in biopsies of 19 human patients (eight of the patients had muscle pain/damage while using statins). The results showed that atrogin-1 expression was significantly higher among the statin users.
(ii) The second experiment studied statins’ effects on cultured muscle cells treated with various concentrations of lovastatin. Compared with control samples, the lovastatin-treated cells became progressively thinner and more damaged. However, the cells lacking the atrogin-1 gene were resistant to statins’ deleterious effects.
(iii) Thirdly statins were tested on zebra fish. These tests also found that lovastatin led to muscle damage and as the lovastatin levels increased, so too was the damage. Again, (as in the cultured muscle cells) fish lacking the atrogin-1 gene were resistant to statin-induced damage.

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