MicroRNA-665 is involved in the regulation of the expression of the cardioprotective cannabinoid receptor CB2 in patients with severe heart failure

Biochem Biophys Res Commun. 2014 Sep 5;451(4):516-21. doi: 10.1016/j.bbrc.2014.08.008. Epub 2014 Aug 9.

Abstract

The myocardial endocannabinoid system has been linked to stress response and cardioprotection. In chronic heart failure (CHF), protective CB2 receptors are markedly up-regulated while CB1 receptors are slightly down-regulated. We here provide evidence that myocardial CB receptors are subject to microRNA regulation. By a combined computational and experimental approach we show that CB1 receptors are regulated by miR-494, and CB2 receptors are targeted by miR-665. Moreover, we demonstrate that in CHF, miR-665 expression is significantly decreased while miR-494 is slightly increased, which is concordant with the previously reported alterations of CB receptors. These results suggest that in CHF, altered expression of specific miRNAs may contribute to a compensatory response of the diseased myocardium.

Keywords: CB1; CB2; Endocannabinoid system; MicroRNA.

MeSH terms

  • Heart Failure / metabolism*
  • Humans
  • MicroRNAs / physiology*
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / metabolism
  • Receptor, Cannabinoid, CB1 / biosynthesis*
  • Receptor, Cannabinoid, CB2 / biosynthesis*

Substances

  • MIRN494 microRNA, human
  • MIRN665 microRNA, human
  • MicroRNAs
  • Receptor, Cannabinoid, CB1
  • Receptor, Cannabinoid, CB2