Reducing in-stent restenosis therapeutic manipulation of miRNA in vascular remodeling and inflammation

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:Montgomery, Dr Jennifer and Robertson, Dr Keith and Baker, Professor Andrew and Diver, Miss Louise and Oldroyd, Dr Keith and Miller, Dr Ashley and McBride, Dr Martin and Dakin, Dr Rachel and Halliday, Dr Crawford and McDonald, Dr Robert and McClure, Dr John and Kennedy, Dr Simon
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 > Institute of Cardiovascular and Medical Sciences
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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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
519431Interrogation and manipulation of miRNA in acute vascular injuryAndrew BakerBritish Heart Foundation (BHF)RG/09/005/27915RI CARDIOVASCULAR & MEDICAL SCIENCES
649211Role of non-coding RNA in vascular pathologyAndrew BakerBritish Heart Foundation (BHF)RG/14/3/30706RI CARDIOVASCULAR & MEDICAL SCIENCES
559881Evaluation of Mirna and their therapeutic potential in a Mouse Model of In-Stent RestenosisAndrew BakerBritish Heart Foundation (BHF)FS/11/12/28673RI CARDIOVASCULAR & MEDICAL SCIENCES
583361BHF Chair of Translational Cardiovascular SciencesAndrew BakerBritish Heart Foundation (BHF)CH/11/2/28733RI CARDIOVASCULAR & MEDICAL SCIENCES