Abstract / Description of output
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 language | English |
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Pages (from-to) | 2314-2327 |
Number of pages | 14 |
Journal | Journal of the American College of Cardiology |
Volume | 65 |
Issue number | 21 |
Early online date | 25 May 2015 |
DOIs | |
Publication status | Published - 2 Jun 2015 |
Keywords / Materials (for Non-textual outputs)
- 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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Andrew Baker
- Deanery of Clinical Sciences - Gustav Born Chair of Vascular Biology
- Centre for Cardiovascular Science
Person: Academic: Research Active