Reducing In-Stent Restenosis: Therapeutic Manipulation of miRNA in Vascular Remodeling and Inflammation

Robert A. McDonald, Crawford A. Halliday, Ashley M. Miller, Louise A. Diver, Rachel S. Dakin, Jennifer Montgomery, Martin W. McBride, Simon Kennedy, John D. McClure, Keith E. Robertson, Gillian Douglas, Keith M. Channon, Keith G. Oldroyd, Andrew H. Baker

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND: Drug-eluting stents reduce the incidence of in-stent restenosis, but they result in delayed arterial healing and are associated with a chronic inflammatory response and hypersensitivity reactions. Identifying novel interventions to enhance wound healing and reduce the inflammatory response may improve long-term clinical outcomes. Micro-ribonucleic acids (miRNAs) are noncoding small ribonucleic acids that play a prominent role in the initiation and resolution of inflammation after vascular injury.

OBJECTIVES: This study sought to identify miRNA regulation and function after implantation of bare-metal and drug-eluting stents.

METHODS: Pig, mouse, and in vitro models were used to investigate the role of miRNA in in-stent restenosis.

RESULTS: We documented a subset of inflammatory miRNAs activated after stenting in pigs, including the miR-21 stem loop miRNAs. Genetic ablation of the miR-21 stem loop attenuated neointimal formation in mice post-stenting. This occurred via enhanced levels of anti-inflammatory M2 macrophages coupled with an impaired sensitivity of smooth muscle cells to respond to vascular activation.

CONCLUSIONS: MiR-21 plays a prominent role in promoting vascular inflammation and remodeling after stent injury. MiRNA-mediated modulation of the inflammatory response post-stenting may have therapeutic potential to accelerate wound healing and enhance the clinical efficacy of stenting.

Original languageEnglish
Pages (from-to)2314-2327
Number of pages14
JournalJournal of the American College of Cardiology
Volume65
Issue number21
Early online date25 May 2015
DOIs
Publication statusPublished - 2 Jun 2015

Keywords

  • Animals
  • Coronary Restenosis
  • Drug-Eluting Stents
  • Inflammation
  • Male
  • Mice, Knockout
  • MicroRNAs
  • Swine
  • Vascular Remodeling
  • Vascular System Injuries
  • late stent thrombosis
  • miRNA stem loop
  • neointima
  • smooth muscle cell

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