Abstract 11: Suppression of Coronary Artery Stent Inflammation by Colchicine Decreases Stent Restenosis, as Assessed by Serial in vivo Optical Molecular-structural Imaging
Background: Restenosis of coronary stents causes substantial morbidity. Inflammation drives restenosis by activating smooth muscle cells to form obstructive neointima. Recent data suggests that colchicine, an anti-proliferative and anti-inflammatory agent, may reduce clinical stent restenosis. Here we assessed the effects of colchicine on in vivo stent-induced inflammatory protease activity and subsequent restenosis using serial intravascular molecular-structural near-infrared fluorescence (NIRF)-optical coherence tomography (OCT) imaging.
Methods: Rabbits implanted with clinical-grade bare-metal stents (3.5x12 mm) received oral colchicine 0.6 mg or placebo daily (N=5 rabbits, 15 stents per group) and were imaged at 2 and 6 weeks with intravascular NIRF-OCT 24 hours following ProSense VM110 (4 mg/kg IV; ex/em 750/780 nm) for molecular NIRF imaging of cathepsin protease inflammatory activity. Neointimal formation was measured every 400 μm by co-registered structural OCT. Stents were analyzed by ex vivo fluorescence microscopy, histology, and cathepsin mRNA expression.
Results: In controls, NIRF inflammation at 2 weeks was significantly enhanced at the stent edges (edge 32.6±7.3 vs. mid 20.1±2.6 nM; p<0.0001) and corresponded to greater stent edge ΔOCT neointimal growth between 2 and 6 weeks (edge 0.61±0.25 vs. mid 0.33±0.13 mm2; p<0.01), providing strong prediction of early NIRF inflammation for subsequent restenosis by OCT (r=0.72; p=0.001). Colchicine significantly decreased 2-week NIRF inflammation (stent TBR: control 2.42±0.10 vs. colchicine 1.69±0.11; p<0.0001), and neutralized the stent edge 6-week neointimal increase observed in controls (colchicine ΔOCT edge 0.05±0.05 vs. mid 0.02±0.03 mm2; p=0.21). Ex vivo analyses corroborated the in vivo results.
Conclusion: We demonstrate that in vivo NIRF inflammatory protease activity predicts stent locations that develop greater restenosis, and that colchicine, an FDA-approved agent, decreases stent-induced inflammation and subsequent restenosis in vivo. lntravascular NIRF-OCT is a novel translatable approach to predict site-specific coronary stent restenosis based on the local inflammatory profile and monitor the effects of anti-restenosis therapeutics.
Author Disclosures: E.A. Osborn: None. G.J. Ughi: None. A. Mauskapf: None. P. Oettgen: None. G.J. Tearney: Other Research Support; Modest; Canon, Merck, Terumo. Consultant/Advisory Board; Modest; Samsung. F.A. Jaffer: Other Research Support; Modest; Merck, Kowa, Siemens. Other; Modest; Boston Scientific.
This research has received full or partial funding support from the American Heart Association.
- © 2015 by American Heart Association, Inc.