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

Article

关键词: MONOCYTE CHEMOATTRACTANT PROTEIN-1;    SMOOTH-MUSCLE-CELLS;    PORCINE CORONARY-ARTERIES;    DRUG-ELUTING STENTS;    CIS-ELEMENT DECOY;    NEOINTIMAL HYPERPLASIA;    GENE-THERAPY;    BALLOON INJURY;    PART II;    MODEL;   

DOI  :  10.1161/CIRCULATIONAHA.105.582254

来源: SCIE

【 摘 要 】

Background - Nuclear factor-kappa B (NF-kappa B) plays a critical role in the vascular response to injury. However, the role of NF-kappa B in the mechanism of in-stent restenosis remains unclear. We therefore tested the hypothesis that blockade of NF-kappa B by stent-based delivery of a cis-element decoy of NF-kappa B reduces in-stent neointimal formation. Methods and Results - Stents were coated with a polymer containing or not containing NF-kappa B decoy, which represented a fast-release formulation (< 7 days). Bare, polymer-coated, and NF-kappa B decoy-eluting stents were implanted in iliac arteries of hypercholesterolemic rabbits. Increased NF-kappa B activity was noted at early stages after stenting, which was suppressed by stent-based delivery of NF-kappa B decoy. NF-kappa B decoy-eluting stents also reduced monocyte infiltration and monocyte chemoattractant protein-1 expression and suppressed CD14 activation on circulating leukocytes. Importantly, NF-kappa B 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-kappa B decoy-eluting stents. Transfection of NF-kappa B decoy suppressed proliferation of human coronary artery smooth muscle cells in vitro. No systemic adverse effects of NF-kappa B decoy were detected. Conclusions - Stent-based local delivery of NF-kappa B 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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