MicroRNAs: Novel Molecular Targets and Response Modulators of Statin Therapy

Trends Pharmacol Sci. 2018 Nov;39(11):967-981. doi: 10.1016/j.tips.2018.09.005. Epub 2018 Sep 21.

Abstract

Cardiovascular disease (CVD) is a major cause of death globally. Addressing cardiovascular risk factors, particularly dyslipidemia, represents the most robust clinical strategy towards reducing the CVD burden. Statins inhibit 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase and represent the main therapeutic approach for lowering cholesterol and reducing plaque formation/rupture. The protective effects of statins extend beyond lowering cholesterol. MicroRNAs (miRNAs or miRs), small noncoding regulatory RNAs, likely mediate the positive pleiotropic effects of statins via modulation of lipid metabolism, enhancement of endothelial function, inhibition of inflammation, improvement of plaque stability, and immune regulation. miRNAs are implicated in statin-related interindividual variations in therapeutic response, directly via HMG-CoA reductase, or indirectly through targeting cytochrome P450 3A (CYP3A) functionality and proprotein convertase subtilisin/kexin type9 (PCSK9) biology.

Keywords: Statins; cardiovascular disease; interindividual variation; microRNAs; pleiotropic effects.

Publication types

  • Review

MeSH terms

  • Animals
  • Cardiovascular Diseases / drug therapy
  • Cardiovascular Diseases / genetics*
  • Endothelial Cells / physiology
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • MicroRNAs*
  • Plaque, Atherosclerotic / drug therapy
  • Plaque, Atherosclerotic / genetics

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • MicroRNAs