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

Armando Ialenti, Gianluca Grassia, Peter Gordon, Marcella Maddaluno, Maria Vittoria Di Lauro, Andrew H Baker, Angelo Guglielmotti, Antonio Colombo, Giuseppe Biondi, Simon Kennedy, Pasquale Maffia

Research output: Contribution to journalArticlepeer-review

Abstract

OBJECTIVE: 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.

METHODS AND RESULTS: 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 μmol/L) reduced tumor necrosis factor-α (50 ng/mL)-induced pig coronary artery smooth muscle cell proliferation and inhibited MCP-1 production.

CONCLUSION: 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.

Original languageEnglish
Pages (from-to)2448-54
Number of pages7
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume31
Issue number11
DOIs
Publication statusPublished - Nov 2011

Keywords

  • Administration, Oral
  • Animals
  • Cell Proliferation
  • Coronary Stenosis
  • Coronary Vessels
  • Indazoles
  • Male
  • Models, Animal
  • Monocyte Chemoattractant Proteins
  • Muscle, Smooth, Vascular
  • Neointima
  • Propionates
  • Stents
  • Swine
  • Treatment Outcome

Fingerprint

Dive into the research topics of 'Inhibition of in-stent stenosis by oral administration of bindarit in porcine coronary arteries'. Together they form a unique fingerprint.

Cite this