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

    Access Status
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    Authors
    Allen, S.
    Mamotte, Cyril
    Date
    2017
    Type
    Journal Article
    
    Metadata
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    Citation
    Allen, S. and Mamotte, C. 2017. Pleiotropic and Adverse Effects of Statins-Do Epigenetics Play a Role? Journal of Pharmacology and Experimental Therapeutics. 362 (2): pp. 319-326.
    Source Title
    Journal of Pharmacology and Experimental Therapeutics
    DOI
    10.1124/jpet.117.242081
    ISSN
    0022-3565
    School
    School of Biomedical Sciences
    URI
    http://hdl.handle.net/20.500.11937/57026
    Collection
    • Curtin Research Publications
    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.

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