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

研究成果: ジャーナルへの寄稿記事

45 引用 (Scopus)

抄録

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.

元の言語英語
ページ(範囲)2773-2779
ページ数7
ジャーナルCirculation
114
発行部数25
DOI
出版物ステータス出版済み - 12 1 2006

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Stents
Rabbits
Polymers
Chemokine CCL2
Iliac Artery
Fibrin
Smooth Muscle Myocytes
Transfection
Blood Vessels
Regeneration
Monocytes
Coronary Vessels
Leukocytes
Hemorrhage
Inflammation
Wounds and Injuries

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

これを引用

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.

:: Circulation, 巻 114, 番号 25, 01.12.2006, p. 2773-2779.

研究成果: ジャーナルへの寄稿記事

ohtani, K, Egashira, K, Nakano, K, Zhao, G, Funakoshi, K, Ihara, Y, Kimura, S, Tominaga, R, Morishita, R & Sunagawa, K 2006, 'Stent-based local delivery of nuclear factor-κB decoy attenuates in-stent restenosis in hypercholesterolemic rabbits', Circulation, 巻. 114, 番号 25, pp. 2773-2779. https://doi.org/10.1161/CIRCULATIONAHA.105.582254
ohtani, kisho ; Egashira, Kensuke ; Nakano, Kaku ; Zhao, Gang ; Funakoshi, Kouta ; Ihara, Yoshiko ; Kimura, Satoshi ; Tominaga, Ryuji ; Morishita, Ryuichi ; Sunagawa, Kenji. / Stent-based local delivery of nuclear factor-κB decoy attenuates in-stent restenosis in hypercholesterolemic rabbits. :: Circulation. 2006 ; 巻 114, 番号 25. pp. 2773-2779.
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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.",
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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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U2 - 10.1161/CIRCULATIONAHA.105.582254

DO - 10.1161/CIRCULATIONAHA.105.582254

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EP - 2779

JO - Circulation

JF - Circulation

SN - 0009-7322

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