期刊
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
卷 65, 期 21, 页码 2314-2327出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jacc.2015.03.549
关键词
late stent thrombosis; miRNA stem loop; neointima; smooth muscle cell
资金
- British Heart Foundation [RG/09/005/27915, RG/14/3/30706, FS11/12/28673]
- British Heart Foundation Chair of Translational Cardiovascular Sciences [CH/11/2/28733]
- National Institute for Health Research Oxford Biomedical Research Centre
- British Heart Foundation [RG/09/005/27915, RG/12/5/29576, FS/11/12/28673, RG/14/3/30706] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0514-10166] Funding Source: researchfish
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. (C) 2015 by the American College of Cardiology Foundation.
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