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 publication

DOI

10.1016/j.jacc.2015.03.549

Type

Journal article

Journal

J Am Coll Cardiol

Publication Date

02/06/2015

Volume

65

Pages

2314 - 2327

Keywords

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