Statins are a popular class of drugs used to successfully combat high cholesterol. However, the rare, but serious, and poorly understood side effect of skeletal muscle breakdown (a process known as atrophy) prevents more prevalent use of these drugs. New insight into the mechanism of statin-induced skeletal muscle atrophy has been provided by reserachers at Beth Israel Deaconess Medical Center, Boston.
In this study, the authors focused on the activity of atrogin-1, a gene highly associated with skeletal muscle atrophy. Following treatment with lovastatin, a commonly prescribed statin, atrogin-1 was induced in cultured mouse muscle cells and in zebrafish embryos. Furthermore, statin-induced muscle injury in the zebrafish was prevented by reducing the amount of atrogin-1 expressed. Finally, when the protein PGC-1a (which protects against skeletal muscle damage and atrophy) was expressed in zebrafish, both atrogin-1 expression and lovastatin-induced muscle damage were prevented. These data led the authors to conclude that atrogin-1 is a critical mediator of statin-induced muscle damage and that inhibiting atrogin-1 function might protect against this unwanted side effect of statins.
TITLE: The muscle-specific ubiquitin ligase atrogin-1/MAFbx mediates statin-induced muscle toxicity
AUTHOR CONTACT:
Stewart H. Lecker,
Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
Phone: (617) 667-2147; Fax: (617) 667-5276; E-mail: slecker@bidmc.harvard.edu
Vikas P. Sukhatme
Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
Phone: (617) 667-2147; Fax: (617) 667-5276; E-mail: vsukhatm@bidmc.harvard.edu
View the PDF of this article at: https://www.the-jci.org/article.php?id=32741
Journal of Clinical Investigation