Stent-based local delivery of nuclear factor-kappaB decoy attenuates in-stent restenosis in hypercholesterolemic rabbits.
BACKGROUND
Nuclear factor-kappaB (NF-kappaB) plays a critical role in the vascular response to injury. However, the role of NF-kappaB in the mechanism of in-stent restenosis remains unclear. We therefore tested the hypothesis that blockade of NF-kappaB by stent-based delivery of a cis-element "decoy" of NF-kappaB reduces in-stent neointimal formation.


RESULTS
Stents were coated with a polymer containing or not containing NF-kappaB decoy, which represented a fast-release formulation (<7 days). Bare, polymer-coated, and NF-kappaB decoy-eluting stents were implanted in iliac arteries of hypercholesterolemic rabbits. Increased NF-kappaB activity was noted at early stages after stenting, which was suppressed by stent-based delivery of NF-kappaB decoy. NF-kappaB decoy-eluting stents also reduced monocyte infiltration and monocyte chemoattractant protein-1 expression and suppressed CD14 activation on circulating leukocytes. Importantly, NF-kappaB 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-kappaB decoy-eluting stents. Transfection of NF-kappaB decoy suppressed proliferation of human coronary artery smooth muscle cells in vitro. No systemic adverse effects of NF-kappaB decoy were detected.


CONCLUSIONS
Stent-based local delivery of NF-kappaB 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.
Ohtani
Kisho
K
Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Egashira
Kensuke
K
Nakano
Kaku
K
Zhao
Gang
G
Funakoshi
Kouta
K
Ihara
Yoshiko
Y
Kimura
Satoshi
S
Tominaga
Ryuji
R
Morishita
Ryuichi
R
Sunagawa
Kenji
K
D015906:Angioplasty, Balloon, Coronary; D000818:Animals; D050197:Atherosclerosis / Q000601:surgery* / Q000628:therapy; D001665:Binding Sites; D023903:Coronary Restenosis / Q000517:prevention & control*; D004195:Disease Models, Animal; D006801:Humans; D006937:Hypercholesterolemia / Q000150:complications*; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015607:Stents
D016328:NF-kappa B