Inhibition of in-stent stenosis by oral administration of bindarit in porcine coronary arteries

Ialenti, A. et al. (2011) Inhibition of in-stent stenosis by oral administration of bindarit in porcine coronary arteries. Arteriosclerosis, Thrombosis, and Vascular Biology, 31(11), pp. 2448-2454. (doi: 10.1161/ATVBAHA.111.230078) (PMID:21852559)




<p><b>Objective:</b> We have previously demonstrated that bindarit, a selective inhibitor of monocyte chemotactic proteins (MCPs), is effective in reducing neointimal formation in rodent models of vascular injury by reducing smooth muscle cell proliferation and migration and neointimal macrophage content, effects associated with the inhibition of MCP-1/CCL2 production. The aim of the current study was to evaluate the efficacy of bindarit on in-stent stenosis in the preclinical porcine coronary stent model.</p> <p><b>Methods and Results:</b> One or 2 bare metal stents (Multi-Link Vision, 3.5 mm) were deployed (1:1.2 oversize ratio) in the coronary arteries of 42 pigs (20 bindarit versus 22 controls). Bindarit (50 mg/kg per day) was administered orally from 2 days before stenting until the time of euthanasia at 7 and 28 days. Bindarit caused a significant reduction in neointimal area (39.4%, P<0.001, n=9 group), neointimal thickness (51%, P<0.001), stenosis area (37%, P<0.001), and inflammatory score (40%, P<0.001) compared with control animals, whereas there was no significant difference in the injury score between the 2 groups. Moreover, treatment with bindarit significantly reduced the number of proliferating cells (by 45%, P<0.05; n=6 group) and monocyte/macrophage content (by 55%, P<0.01; n=5–6 group) in stented arteries at day 7 and 28, respectively. These effects were associated with a significant (P<0.05) reduction of MCP-1 plasma levels at day 28. In vitro data showed that bindarit (10–300 micromol/L) reduced tumor necrosis factor-alpha (50 ng/mL)–induced pig coronary artery smooth muscle cell proliferation and inhibited MCP-1 production.</p> <p><b>Conclusion:</b> Our results show the efficacy of bindarit in the prevention of porcine in-stent stenosis and support further investigation for clinical application of this compound.</p>

Item Type:Articles
Glasgow Author(s) Enlighten ID:Baker, Professor Andrew and Kennedy, Professor Simon and Maffia, Professor Pasquale and Grassia, Dr Gianluca
Authors: Ialenti, A., Grassia, G., Gordon, P., Maddaluno, M., Di Lauro, M.V., Baker, A.H., Guglielmotti, A., Colombo, A., Biondi, G., Kennedy, S., and Maffia, P.
Subjects:R Medicine > RM Therapeutics. Pharmacology
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Arteriosclerosis, Thrombosis, and Vascular Biology
Publisher:American Heart Association
ISSN (Online):1524-4636
Published Online:18 August 2011
Copyright Holders:Copyright © 2011 American Heart Association
First Published:First published in Arteriosclerosis, Thrombosis, and Vascular Biology 31(11):2448-2454
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
497764BINDARIT STUDYPasquale MaffiaAngelini I Santa Palomba Research and Enterprise (ACRAF)004FA10335III -IMMUNOLOGY