microRNAs and HDL life cycle

Cardiovasc Res. 2014 Aug 1;103(3):414-22. doi: 10.1093/cvr/cvu140. Epub 2014 Jun 3.

Abstract

miRNAs have emerged as important regulators of lipoprotein metabolism. Work over the past few years has demonstrated that miRNAs control the expression of most of the genes associated with high-density lipoprotein (HDL) metabolism, including the ATP transporters, ABCA1 and ABCG1, and the scavenger receptor SRB1. These findings strongly suggest that miRNAs regulate HDL biogenesis, cellular cholesterol efflux, and HDL cholesterol (HDL-C) uptake in the liver, thereby controlling all of the steps of reverse cholesterol transport. Recent work in animal models has demonstrated that manipulating miRNA levels including miR-33 can increase circulating HDL-C. Importantly, antagonizing miR-33 in vivo enhances the regression and reduces the progression of atherosclerosis. These findings support the idea of developing miRNA inhibitors for the treatment of dyslipidaemia and related cardiovascular disorders such as atherosclerosis. This review article focuses on how HDL metabolism is regulated by miRNAs and how antagonizing miRNA expression could be a potential therapy for treating cardiometabolic diseases.

Keywords: ABCA1 and SRB1; Cholesterol metabolism; MiRNAs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • ATP Binding Cassette Transporter 1 / genetics
  • ATP Binding Cassette Transporter 1 / metabolism
  • ATP Binding Cassette Transporter, Subfamily G, Member 1
  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / metabolism
  • Animals
  • Atherosclerosis / blood
  • Atherosclerosis / diagnosis
  • Atherosclerosis / metabolism*
  • Atherosclerosis / prevention & control
  • Cholesterol, HDL / metabolism
  • Dyslipidemias / blood
  • Dyslipidemias / diagnosis
  • Dyslipidemias / metabolism*
  • Dyslipidemias / therapy
  • Gene Expression Regulation
  • Humans
  • Lipoproteins, HDL / blood
  • Lipoproteins, HDL / genetics
  • Lipoproteins, HDL / metabolism*
  • MicroRNAs / blood
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Oligonucleotides, Antisense / therapeutic use
  • Scavenger Receptors, Class B / genetics
  • Scavenger Receptors, Class B / metabolism
  • Transcription, Genetic

Substances

  • ABCA1 protein, human
  • ABCG1 protein, human
  • ATP Binding Cassette Transporter 1
  • ATP Binding Cassette Transporter, Subfamily G, Member 1
  • ATP-Binding Cassette Transporters
  • Cholesterol, HDL
  • Lipoproteins, HDL
  • MicroRNAs
  • Oligonucleotides, Antisense
  • SCARB1 protein, human
  • Scavenger Receptors, Class B