Stent-based local delivery of nuclear factor-κB decoy attenuates in-stent restenosis in hypercholesterolemic rabbits

Kisho Ohtani, Kensuke Egashira, Kaku Nakano, Gang Zhao, Kouta Funakoshi, Yoshiko Ihara, Satoshi Kimura, Ryuji Tominaga, Ryuichi Morishita, Kenji Sunagawa

Research output: Contribution to journalArticlepeer-review

47 Citations (Scopus)

Abstract

BACKGROUND - Nuclear factor-κB (NF-κB) plays a critical role in the vascular response to injury. However, the role of NF-κB in the mechanism of in-stent restenosis remains unclear. We therefore tested the hypothesis that blockade of NF-κB by stent-based delivery of a cis-element "decoy" of NF-κB reduces in-stent neointimal formation. METHODS AND RESULTS - Stents were coated with a polymer containing or not containing NF-κB decoy, which represented a fast-release formulation (<7 days). Bare, polymer-coated, and NF-κB decoy-eluting stents were implanted in iliac arteries of hypercholesterolemic rabbits. Increased NF-κB activity was noted at early stages after stenting, which was suppressed by stent-based delivery of NF-κB decoy. NF-κB decoy-eluting stents also reduced monocyte infiltration and monocyte chemoattractant protein-1 expression and suppressed CD14 activation on circulating leukocytes. Importantly, NF-κB decoy-eluting stents attenuated neointimal formation on day 28. There was no evidence of an incomplete healing process (persistent inflammation, hemorrhage, fibrin deposition, impaired endothelial regeneration) at the site of NF-κB decoy-eluting stents. Transfection of NF-κB decoy suppressed proliferation of human coronary artery smooth muscle cells in vitro. No systemic adverse effects of NF-κB decoy were detected. CONCLUSIONS - Stent-based local delivery of NF-κB decoy reduced in-stent neointimal formation with no evidence of incomplete healing. These data suggest that this strategy may be a practical and promising means for prevention of in-stent restenosis in humans.

Original languageEnglish
Pages (from-to)2773-2779
Number of pages7
JournalCirculation
Volume114
Issue number25
DOIs
Publication statusPublished - Dec 2006

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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