miR-29a attenuates cardiac hypertrophy through inhibition of PPARδ expression

J Cell Physiol. 2019 Aug;234(8):13252-13262. doi: 10.1002/jcp.27997. Epub 2018 Dec 23.

Abstract

Although cardiac hypertrophy is widely recognized as a risk factor that leads to cardiac dysfunction and, ultimately, heart failure, the complex mechanisms underlying cardiac hypertrophy remain incompletely characterized. The nuclear receptor peroxisome proliferator-activated receptor δ (PPARδ) is involved in the regulation of cardiac lipid metabolism. Here, we describe a novel PPARδ-dependent molecular cascade involving microRNA-29a (miR-29a) and atrial natriuretic factor (ANF), which is reactivated in cardiac hypertrophy. In addition, we identify a novel role of miR-29a, in which it has a cardioprotective function in isoproterenol hydrochloride-induced cardiac hypertrophy by targeting PPARδ and downregulating ANF. Finally, we provide evidence that miR-29a reduces the isoproterenol hydrochloride-induced cardiac hypertrophy response, thereby underlining the potential clinical relevance of miR-29a in which it may serve as a potent therapeutic target for heart hypertrophy treatment.

Keywords: cardiac hypertrophy; microRNA; nuclear receptor PPARδ; isoproterenol hydrochloride; transcriptional regulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atrial Natriuretic Factor / metabolism*
  • Cardiomegaly / metabolism*
  • Down-Regulation
  • Gene Expression Regulation / physiology*
  • Mice
  • Mice, Inbred ICR
  • MicroRNAs / metabolism*
  • Myocytes, Cardiac / metabolism
  • Receptors, Cytoplasmic and Nuclear / metabolism*

Substances

  • MIRN29 microRNA, mouse
  • MicroRNAs
  • Ppard protein, mouse
  • Receptors, Cytoplasmic and Nuclear
  • Atrial Natriuretic Factor