Reducing in-stent restenosis: therapeutic manipulation of miRNA in vascular remodeling and inflammation
RA McDonald, CA Halliday, AM Miller, LA Diver… - Journal of the American …, 2015 - jacc.org
RA McDonald, CA Halliday, AM Miller, LA Diver, RS Dakin, J Montgomery, MW McBride…
Journal of the American College of Cardiology, 2015•jacc.orgBackground: 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 …
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 …
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.
jacc.org