On the ability of imatinib mesylate to inhibit smooth muscle cell proliferation without delaying endothelialization: an in vitro study.
Restenosis, the re-occlusion of a diseased vessel following a surgical intervention, is a major cause of failure of angioplasty, stenting, and bypass grafting with natural and synthetic vessels. In healthy vessels, the endothelium exerts a control over smooth muscle cell (SMC) proliferation and migration. Unfortunately, revascularization procedures damage the endothelium of natural vessels and bypass vessels are completely devoid of endothelial cells. Many strategies have been developed to inhibit SMC proliferation and reduce intimal hyperplasia, yet most of the drugs tested thus far simultaneously inhibit endothelialization and do not selectively target SMCs. The ideal biological agent should have anti-proliferative effects on SMCs while preserving vascular healing and endothelialization so as to prevent late thrombosis. Imatinib mesylate is a specific inhibitor of three tyrosine kinase receptors, two of which, PDGF-R and c-Kit, are implicated in the pathogenesis of intimal hyperplasia. In this study, we investigated in vitro the potential of imatinib mesylate to inhibit SMCs and its effect on ECs. Our findings indicate that low doses of imatinib mesylate successfully inhibit SMC proliferation. Furthermore, at these concentrations, the drug was not only harmless to ECs, but also enhanced their proliferation. In light of these in vitro results, imatinib mesylate shows potential as a good candidate to inhibit intimal hyperplasia without delaying neo-endothelialization.
Vallières
Karine
K
Laboratoire d'Ingénierie de Surface, Centre de Recherche sur les Matériaux Avancés, Département de Génie des Mines, de la Métallurgie et des Matériaux, Faculté des Sciences et Génie, Université Laval, Québec, QC G1V0A6, Canada.
Petitclerc
Eric
E
Laroche
Gaétan
G
D000818:Animals; D001549:Benzamides; D002417:Cattle; D049109:Cell Proliferation / Q000187:drug effects*; D018920:Coculture Techniques; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D000068877:Imatinib Mesylate; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000502:physiology*; D010879:Piperazines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*
D001549:Benzamides; D006131:Growth Inhibitors; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate