Abstract 11429: Bindarit, an Inhibitor of Monocyte Chemoattractant Proteins (MCPs) Production, Reduces in-Stent Restenosis in Porcine Coronary Arteries
Background and Purpose: Bindarit is an original anti-inflammatory compound able to selectively inhibit the production of a subfamily of CC inflammatory chemokines, including MCP-1/CCL2, MCP-3/CCL7 and MCP-2/CCL8. Previous results have demonstrated that bindarit attenuates neointima formation in the rat balloon angioplasty model and in a model of wire-induced injury in ApoE-/- mice by inhibiting vascular smooth muscle cell (SMC) proliferation and migration and reducing macrophage number in neointima: effects associated with the inhibition of MCP-1/CCL2 production. In the current study, we investigated the effect of bindarit on in-stent restenosis in a porcine coronary stent model.
Methods: One or two bare metal stents (Multi-Link Vision, 3.5 mm) were deployed (1:1.2 oversize ratio) in the coronary arteries of 18 pigs (n=9/bindarit group; n=9/control group). Bindarit (50 mg/kg/day) or placebo was administered orally from 2 days before stenting until the time of euthanasia at 28 days after stenting. A total of 31 stents (16 from bindarit pigs and 15 from control pigs) were embedded in resin, cut and polished using a diamond saw and stained using heamatoxylin and eosin.
Results: Morphometric assessment of stent-section showed significant reduction in neointimal area (4.0±0.46mm2 vs 6.7±0.44mm2, p<0.01) neointimal thickness (270.2±26.92μm vs 551.1±49.94μm, p<0.001) stenosis area (47.6±3.42% vs 75.0±2.71%, p<0.001), and inflammatory score (1.1±0.06 vs 1.8±0.11, p<0.001) in the bindarit-treated group compared to control animals, whereas there was no significant difference in the injury score between the two groups (2.3±0.11 vs 2.2±0.13). These effects were associated with a significant (30%) reduction of MCP-1 plasma levels at day 28. In addition, in vitro data show that bindarit (10–300 μM) reduced TNF-α (50 ng/ml) induced pig coronary artery SMC proliferation by significantly inhibiting MCP-1 production.
Conclusions: Our results show the efficacy of bindarit in the prevention of in-stent restenosis and offer a clue for its potential clinical application.
- © 2010 by American Heart Association, Inc.