Local MicroRNA Modulation Using a Novel Anti-miR-21-Eluting Stent Effectively Prevents Experimental In-Stent Restenosis

Arterioscler Thromb Vasc Biol. 2015 Sep;35(9):1945-53. doi: 10.1161/ATVBAHA.115.305597. Epub 2015 Jul 16.


Objective: Despite advances in stent technology for vascular interventions, in-stent restenosis (ISR) because of myointimal hyperplasia remains a major complication.

Approach and results: We investigated the regulatory role of microRNAs in myointimal hyperplasia/ISR, using a humanized animal model in which balloon-injured human internal mammary arteries with or without stenting were transplanted into Rowett nude rats, followed by microRNA profiling. miR-21 was the only significantly upregulated candidate. In addition, miR-21 expression was increased in human tissue samples from patients with ISR compared with coronary artery disease specimen. We systemically repressed miR-21 via intravenous fluorescein-tagged-locked nucleic acid-anti-miR-21 (anti-21) in our humanized myointimal hyperplasia model. As expected, suppression of vascular miR-21 correlated dose dependently with reduced luminal obliteration. Furthermore, anti-21 did not impede reendothelialization. However, systemic anti-miR-21 had substantial off-target effects, lowering miR-21 expression in liver, heart, lung, and kidney with concomitant increase in serum creatinine levels. We therefore assessed the feasibility of local miR-21 suppression using anti-21-coated stents. Compared with bare-metal stents, anti-21-coated stents effectively reduced ISR, whereas no significant off-target effects could be observed.

Conclusion: This study demonstrates the efficacy of an anti-miR-coated stent for the reduction of ISR.

Keywords: coronary restenosis; hyperplasia; microRNAs; rats; stents.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Antinuclear / pharmacology*
  • Cell Proliferation / drug effects
  • Coated Materials, Biocompatible*
  • Coronary Restenosis / genetics
  • Coronary Restenosis / metabolism
  • Coronary Restenosis / prevention & control*
  • Coronary Vessels / drug effects
  • Coronary Vessels / metabolism
  • Coronary Vessels / ultrastructure
  • Disease Models, Animal
  • Drug-Eluting Stents
  • Female
  • Gene Expression Regulation*
  • Graft Occlusion, Vascular / genetics
  • Graft Occlusion, Vascular / metabolism
  • Graft Occlusion, Vascular / prevention & control*
  • Humans
  • Male
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics*
  • MicroRNAs / immunology
  • Microscopy, Electron, Scanning
  • Middle Aged
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / ultrastructure
  • Neointima / metabolism
  • Neointima / pathology
  • Prosthesis Design
  • Rats
  • Rats, Nude


  • Antibodies, Antinuclear
  • Coated Materials, Biocompatible
  • MIRN21 microRNA, mouse
  • MicroRNAs