title: Reducing In-Stent Restenosis: Therapeutic Manipulation of miRNA in Vascular Remodeling and Inflammation.
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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, Scotland.
authors.forename: Robert A
authors.initials: RA
authors.lastname: McDonald
authors.affiliation: Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, Scotland.
authors.forename: Crawford A
authors.initials: CA
authors.lastname: Halliday
authors.affiliation: Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, Scotland.
authors.forename: Ashley M
authors.initials: AM
authors.lastname: Miller
authors.affiliation: Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, Scotland.
authors.forename: Louise A
authors.initials: LA
authors.lastname: Diver
authors.affiliation: Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, Scotland.
authors.forename: Rachel S
authors.initials: RS
authors.lastname: Dakin
authors.affiliation: Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, Scotland.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Montgomery
authors.affiliation: Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, Scotland.
authors.forename: Martin W
authors.initials: MW
authors.lastname: McBride
authors.affiliation: Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, Scotland.
authors.forename: Simon
authors.initials: S
authors.lastname: Kennedy
authors.affiliation: Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, Scotland.
authors.forename: John D
authors.initials: JD
authors.lastname: McClure
authors.affiliation: Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, Scotland.
authors.forename: Keith E
authors.initials: KE
authors.lastname: Robertson
authors.affiliation: West of Scotland Regional Heart & Lung Centre, Golden Jubilee National Hospital, Clydebank, Scotland.
authors.forename: Gillian
authors.initials: G
authors.lastname: Douglas
authors.affiliation: West of Scotland Regional Heart & Lung Centre, Golden Jubilee National Hospital, Clydebank, Scotland.
authors.forename: Keith M
authors.initials: KM
authors.lastname: Channon
authors.affiliation: Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
authors.forename: Keith G
authors.initials: KG
authors.lastname: Oldroyd
authors.affiliation: Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, Scotland. Electronic address: andrew.h.baker@glasgow.ac.uk.
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Baker
mesh_terms: D000818:Animals; D023903:Coronary Restenosis / Q000378:metabolism* / Q000517:prevention & control; D054855:Drug-Eluting Stents; D007249:Inflammation / Q000378:metabolism; D008297:Male; D018345:Mice, Knockout; D035683:MicroRNAs / Q000378:metabolism*; D013552:Swine; D066253:Vascular Remodeling; D057772:Vascular System Injuries / Q000378:metabolism*
chemical_list: D035683:MicroRNAs; C531950:MIRN21 microRNA, mouse
keywords: late stent thrombosis; miRNA stem loop; neointima; smooth muscle cell