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Research ArticleMinireview

Pleiotropic and Adverse Effects of Statins—Do Epigenetics Play a Role?

Stephanie C. Allen and Cyril D.S. Mamotte
Journal of Pharmacology and Experimental Therapeutics August 2017, 362 (2) 319-326; DOI: https://doi.org/10.1124/jpet.117.242081
Stephanie C. Allen
School of Biomedical Sciences and Curtin Health Innovation Research Institute, Curtin University, Perth, Western Australia
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Cyril D.S. Mamotte
School of Biomedical Sciences and Curtin Health Innovation Research Institute, Curtin University, Perth, Western Australia
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Abstract

Statins are widely used to prevent major cardiovascular events by lowering serum cholesterol. There is evidence that statins have pleiotropic effects—that is, cholesterol-independent effects—that may also confer protection from cardiovascular disease and potentially numerous other pathologies, including cancer. Statins also have a number of well described adverse effects, including myopathy, rhabdomyolysis, liver damage, and type 2 diabetes. This paper examines the evidence of epigenetic modifications as a contributory factor to the pleiotropic and adverse effects of statins. In vitro and animal studies have shown that statins can inhibit histone deacetylase activity and increase histone acetylation. Similarly, there is evidence that statins may inhibit both histone and DNA methyltransferases and subsequently demethylate histone residues and DNA, respectively. These changes have been shown to alter expression of various genes, including tumor suppressor genes and genes thought to have anti-atherosclerotic actions. Statins have also been shown to influence the expression of numerous microRNAs that suppress the translation of proteins involved in tumorigenesis and vascular function. Whether the adverse effects of statins may also have an epigenetic component has been less widely studied, although there is evidence that microRNA expression may be altered in statin-induced muscle and liver damage. As epigenetics and microRNAs influence gene expression, these changes could contribute to the pleiotropic and adverse effects of statins and have long-lasting effects on the health of statin users.

Footnotes

    • Received April 10, 2017.
    • Accepted May 23, 2017.
  • https://doi.org/10.1124/jpet.117.242081.

  • Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 362 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 362, Issue 2
1 Aug 2017
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Research ArticleMinireview

Epigenetic Effects of Statins

Stephanie C. Allen and Cyril D.S. Mamotte
Journal of Pharmacology and Experimental Therapeutics August 1, 2017, 362 (2) 319-326; DOI: https://doi.org/10.1124/jpet.117.242081

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Research ArticleMinireview

Epigenetic Effects of Statins

Stephanie C. Allen and Cyril D.S. Mamotte
Journal of Pharmacology and Experimental Therapeutics August 1, 2017, 362 (2) 319-326; DOI: https://doi.org/10.1124/jpet.117.242081
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    • Abstract
    • Introduction
    • The Nature of Epigenetic Modifications
    • Epigenetic Effects of Statins
    • Epigenetics as a Mechanism for the Pleiotropic Effects of Statins
    • Epigenetics in Liver and Muscle Toxicity
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