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 language | English |
|---|---|
| Pages (from-to) | 2773-2779 |
| Number of pages | 7 |
| Journal | Circulation |
| Volume | 114 |
| Issue number | 25 |
| DOIs | |
| Publication status | Published - Dec 1 2006 |
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All Science Journal Classification (ASJC) codes
- Cardiology and Cardiovascular Medicine
- Physiology (medical)
Cite this
Stent-based local delivery of nuclear factor-κB decoy attenuates in-stent restenosis in hypercholesterolemic rabbits. / Ohtani, Kisho; Egashira, Kensuke; Nakano, Kaku; Zhao, Gang; Funakoshi, Kouta; Ihara, Yoshiko; Kimura, Satoshi; Tominaga, Ryuji; Morishita, Ryuichi; Sunagawa, Kenji.
In: Circulation, Vol. 114, No. 25, 01.12.2006, p. 2773-2779.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Stent-based local delivery of nuclear factor-κB decoy attenuates in-stent restenosis in hypercholesterolemic rabbits
AU - Ohtani, Kisho
AU - Egashira, Kensuke
AU - Nakano, Kaku
AU - Zhao, Gang
AU - Funakoshi, Kouta
AU - Ihara, Yoshiko
AU - Kimura, Satoshi
AU - Tominaga, Ryuji
AU - Morishita, Ryuichi
AU - Sunagawa, Kenji
PY - 2006/12/1
Y1 - 2006/12/1
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=33845909835&partnerID=8YFLogxK
U2 - 10.1161/CIRCULATIONAHA.105.582254
DO - 10.1161/CIRCULATIONAHA.105.582254
M3 - Article
C2 - 17130346
AN - SCOPUS:33845909835
VL - 114
SP - 2773
EP - 2779
JO - Circulation
JF - Circulation
SN - 0009-7322
IS - 25
ER -