Long Noncoding RNAs in Atherosclerosis and Vascular Injury: Pathobiology, Biomarkers, and Targets for Therapy

Arterioscler Thromb Vasc Biol. 2020 Sep;40(9):2002-2017. doi: 10.1161/ATVBAHA.120.314222. Epub 2020 Jul 23.

Abstract

Despite major advances in the primary and secondary prevention of atherosclerosis and its risk factors, atherosclerotic cardiovascular disease remains a major clinical and financial burden on individuals and health systems worldwide. In addition, neointima formation and proliferation due to mechanical trauma to the vessel wall during percutaneous coronary interventions can lead to vascular restenosis and limit the longevity and effectiveness of coronary revascularization. Long noncoding RNAs (lncRNAs) have emerged as a novel class of epigenetic regulators with critical roles in the pathogenesis of atherosclerosis and restenosis following vascular injury. Here, we provide an in-depth review of lncRNAs that regulate the development of atherosclerosis or contribute to the pathogenesis of restenosis following mechanical vascular injury. We describe the diverse array of intracellular mechanisms by which lncRNAs exert their regulatory effects. We highlight the utility and challenges of lncRNAs as biomarkers. Finally, we discuss the immense translational potential of lncRNAs and strategies for targeting them therapeutically using oligonucleotide-based therapeutics and novel gene therapy platforms.

Keywords: atherosclerosis; biomarkers; cardiovascular diseases; oligonucleotides; percutaneous coronary intervention.

Publication types

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

MeSH terms

  • Animals
  • Arteries / metabolism*
  • Arteries / pathology
  • Atherosclerosis / genetics
  • Atherosclerosis / metabolism*
  • Atherosclerosis / pathology
  • Atherosclerosis / therapy
  • Constriction, Pathologic
  • Epigenesis, Genetic
  • Genetic Markers
  • Humans
  • Oligonucleotides, Antisense / therapeutic use
  • Plaque, Atherosclerotic
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • RNA, Long Noncoding / therapeutic use
  • RNAi Therapeutics
  • Signal Transduction
  • Vascular Remodeling
  • Vascular System Injuries / genetics
  • Vascular System Injuries / metabolism*
  • Vascular System Injuries / pathology
  • Vascular System Injuries / therapy

Substances

  • Genetic Markers
  • Oligonucleotides, Antisense
  • RNA, Long Noncoding