McDonald, R. A. et al. (2015) Reducing in-stent restenosis therapeutic manipulation of miRNA in vascular remodeling and inflammation. Journal of the American College of Cardiology, 65(21), pp. 2314-2327. (doi: 10.1016/j.jacc.2015.03.549) (PMID:26022821) (PMCID:PMC4444526)
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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.<p></p> Objectives: This study sought to identify miRNA regulation and function after implantation of bare-metal and drug-eluting stents.<p></p> Methods: Pig, mouse, and in vitro models were used to investigate the role of miRNA in in-stent restenosis.<p></p> 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.<p></p> 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.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Robertson, Dr Keith and Baker, Professor Andrew and Miller, Dr Ashley and McBride, Dr Martin and Dakin, Dr Rachel and McDonald, Dr Robert and Kennedy, Professor Simon and Montgomery, Dr Jennifer and Diver, Miss Louise and Oldroyd, Dr Keith and Halliday, Dr Crawford and McClure, Dr John |
| Authors: | McDonald, R. A., Halliday, C. A., Miller, A. M., Diver, L. A., Dakin, R. S., Montgomery, J., McBride, M. W., Kennedy, S., McClure, J. D., Robertson, K. E., Douglas, G., Channon, K. M., Oldroyd, K., and Baker, A. H. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health |
| Journal Name: | Journal of the American College of Cardiology |
| Publisher: | Elsevier Inc. |
| ISSN: | 0735-1097 |
| ISSN (Online): | 1558-3597 |
| Copyright Holders: | Copyright © 2015 American College of Cardiology Foundation |
| First Published: | First published in Journal of the American College of Cardiology 65(21):2314-2327 |
| Publisher Policy: | Reproduced in accordance with the copyright policy of the publisher |
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