Bindarit inhibits human coronary artery smooth muscle cell proliferation, migration and phenotypic switching

Maddaluno, M. et al. (2012) Bindarit inhibits human coronary artery smooth muscle cell proliferation, migration and phenotypic switching. PLoS ONE, 7(10), e47464. (doi:10.1371/journal.pone.0047464) (PMID:23077623) (PMCID:PMC3471825)

[img]
Preview
Text
75045.pdf - Published Version
Available under License Creative Commons Attribution.

5MB

Abstract

Bindarit, a selective inhibitor of monocyte chemotactic proteins (MCPs) synthesis, reduces neointimal formation in animal models of vascular injury and recently has been shown to inhibit in-stent late loss in a placebo-controlled phase II clinical trial. However, the mechanisms underlying the efficacy of bindarit in controlling neointimal formation/restenosis have not been fully elucidated. Therefore, we investigated the effect of bindarit on human coronary smooth muscle cells activation, drawing attention to the phenotypic modulation process, focusing on contractile proteins expression as well as proliferation and migration. The expression of contractile proteins was evaluated by western blot analysis on cultured human coronary smooth muscle cells stimulated with TNF-α (30 ng/mL) or fetal bovine serum (5%). Bindarit (100-300 µM) reduced the embryonic form of smooth muscle myosin heavy chain while increased smooth muscle α-actin and calponin in both TNF-α- and fetal bovine serum-stimulated cells. These effects were associated with the inhibition of human coronary smooth muscle cell proliferation/migration and both MCP-1 and MCP-3 production. The effect of bindarit on smooth muscle cells phenotypic switching was confirmed in vivo in the rat balloon angioplasty model. Bindarit (200 mg/Kg/day) significantly reduced the expression of the embryonic form of smooth muscle myosin heavy chain, and increased smooth muscle α-actin and calponin in the rat carodid arteries subjected to endothelial denudation. Our results demonstrate that bindarit induces the differentiated state of human coronary smooth muscle cells, suggesting a novel underlying mechanisms by which this drug inhibits neointimal formation.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Maffia, Dr Pasquale and Grassia, Dr Gianluca
Authors: Maddaluno, M., Grassia, G., Di Lauro, M.V., Parisi, A., Maione, F., Cicala, C., De Filippis, D., Iuvone, T., Guglielmotti, A., Maffia, P., Mascolo, N., and Ialenti, A.
Subjects:R Medicine > RM Therapeutics. Pharmacology
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:PLoS ONE
Publisher:Public Library of Science
ISSN:1932-6203
Published Online:15 October 2012
Copyright Holders:Copyright © 2012 The Authors
First Published:First published in PLoS ONE 7(10):e47464
Publisher Policy:Reproduced under a Creative Commons License

University Staff: Request a correction | Enlighten Editors: Update this record