• Nooshin Mohammadzadeh, Fabrizio Montecucco, Federico Carbone, Suowen Xu, Khalid Al-Rasadi, and Amirhossein Sahebkar.
• School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
• Eur. J. Clin. Invest. 2020 Dec 1; 50 (12): e13388.

BackgroundEpigenetic events involving the methylation of CpG cites in DNA, histone modifications and noncoding RNAs correlated with many essential processes in human cells and diseases, such as cancer and cardiovascular diseases. HMG-CoA reductase inhibitors (statins)-the LDL cholesterol-lowering drugs-are broadly used in cardio- and cerebro-vascular diseases. It is well established that statins exert pleiotropic functions, but how they exert effects on epigenetic modifications independently of HMG-CoA reductase inhibition is not yet clear. Thereby, understanding these mechanisms may pave the way for further clinical application of statin therapy.DesignFollowing and electronic database search, studies reporting substantial effects of statins on epigenetic reprogramming in both cultured cells and in vivo models were retrieved and reviewed.ResultsEpigenetic mechanisms play an essential role in cellular development and function, and data collected in the past few years have revealed that many of the pleiotropic properties of statins are mediated by epigenetic mechanisms. Furthermore, those 'nonclassical' effects are not limited to CV field but they would extend to other conditions such as malignancies.ConclusionThis review suggests that the epigenetic effects of statins mediate, at least in part, the pleiotropic actions of these drugs but further validation of such effects in clinical studies is yet to be provided.© 2020 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.

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