A hypothetical scheme of statin-induced blockade of mevalonate biosynthesis and its consequences for skeletal muscle gene expression and myopathy. Potential differences in inter-organ uptake, metabolism, and flux of statins in genetically susceptible patients lead to greater skeletal muscle toxicity. Inhibition of mevalonate and its downstream reaction products result in reduced availability of geranylpyrophosphate and farnesyl-pyrophosphate, needed for prenylation/lipidation of signaling proteins. Altered signal transduction pathways reprogram skeletal muscle gene expression. Genetic polymorphisms and significantly altered genes that putatively underpin skeletal muscle pathology are indicated.
Reproduced from: Elam MB, Majumdar G, Mozhui K, et al. Patients experiencing statin-induced myalgia exhibit a unique program of skeletal muscle gene expression following statin re-challenge. PLoS One 2017; 12:e0181308. Available at:
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0181308 (Accessed on November 9, 2017). Copyright © 2017 Elam MB, Majumdar G, Mozhui K, et al. Reproduced under the terms of the
Creative Commons Attribution License. Original figure published in: Norata GD, Tibolla G, Catapano AL. Statins and skeletal muscles toxicity: From clinical trials to everyday practice. Pharmacol Res 2014; 88:107. Illustration modified with the permission of Elsevier Inc. All rights reserved.
