Nucleic Acid-Based Therapies for Atherosclerosis

Curr Atheroscler Rep. 2020 Feb 7;22(2):10. doi: 10.1007/s11883-020-0826-2.

Abstract

Purpose of review: Atherosclerosis is characterized by accumulation of lipids and chronic inflammation in medium size to large arteries. Recently, RNA-based antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs) are being developed, along with small molecule-based drugs and monoclonal antibodies, for the treatment of risk factors associated with atherosclerosis.. The purpose of this review is to describe nucleic acid-based therapeutics and introduce novel RNAs that might become future tools for treatment of atherosclerosis.

Recent findings: RNA-based inhibitors for PCSK9, Lp(a), ApoCIII, and ANGPTL3 have been successfully tested in phase II-III clinical trials. Moreover, multiple microRNA and long non-coding RNAs have been found to reduce atherogenesis in preclinical animal models. Clinical trials especially with ASOs and siRNAs directed to liver, targeting cholesterol and lipoprotein metabolism, have shown promising results. Additional research in larger patient cohorts is needed to fully evaluate the therapeutic potential of these new drugs.

Keywords: Antisense oligonucleotide; Atherosclerosis; Nucleic acid; RNA; siRNA.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Angiopoietin-Like Protein 3
  • Angiopoietin-like Proteins / antagonists & inhibitors
  • Animals
  • Anticholesteremic Agents / therapeutic use*
  • Apolipoprotein C-III / antagonists & inhibitors
  • Atherosclerosis / drug therapy*
  • Atherosclerosis / metabolism
  • Humans
  • Lipoprotein(a) / antagonists & inhibitors
  • Lipoprotein(a) / metabolism
  • Liver / metabolism
  • MicroRNAs / therapeutic use*
  • Oligonucleotides, Antisense / pharmacology
  • Oligonucleotides, Antisense / therapeutic use*
  • PCSK9 Inhibitors
  • RNA, Long Noncoding / therapeutic use*
  • RNA, Small Interfering / pharmacology
  • RNA, Small Interfering / therapeutic use*

Substances

  • ANGPTL3 protein, human
  • APOC3 protein, human
  • Angiopoietin-Like Protein 3
  • Angiopoietin-like Proteins
  • Anticholesteremic Agents
  • Apolipoprotein C-III
  • Lipoprotein(a)
  • MicroRNAs
  • Oligonucleotides, Antisense
  • PCSK9 Inhibitors
  • RNA, Long Noncoding
  • RNA, Small Interfering
  • PCSK9 protein, human