The Tohoku Journal of Experimental Medicine
Online ISSN : 1349-3329
Print ISSN : 0040-8727
ISSN-L : 0040-8727
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Imatinib Mesilate Inhibits Neointimal Hyperplasia via Growth Inhibition of Vascular Smooth Muscle Cells in a Rat Model of Balloon Injury
Yashiro MakiyamaKen TobaKiminori KatoSatoru HironoTakuya OzawaTakashi SaigawaShiro MinagawaManabu IsodaFuyuki AsamiNoboru IkarashiMasato OdaMasato MoriyamaMasutaka HigashimuraToshiki KitajimaKeita OtakiYoshifusa Aizawa
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2008 Volume 215 Issue 4 Pages 299-306

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Abstract

Restenosis is a major problem in percutaneous catheter intervension (PCI) for coronary artery stenosis in patients with acute myocardial infarction. Coronary restenosis arises from intimal hyperplasia, i.e., hyperplasia of the vascular smooth muscle cells (SMCs) caused by endothelial cell (EC) damage due to PCI. Drug eluting stent (DES), a novel stent coated with a cell-growth inhibitor, such as rapamycin, has been utilized to block SMC proliferation, but DES also blocks EC repair and thus requires the administration of anti-platelets for a long time to prevent thrombus formation after PCI. Moreover, insufficient prevention of platelet aggregation sometimes induces restenosis after PCI. One of the signal transduction inhibitors, imatinib mesilate, blocks tyrosine kinase activity of platelet-derived growth factor receptor (PDGFR), and therefore it may block the development of neointima through growth inhibition of SMCs without the obstructive effect on EC-repair. We therefore studied the effects of imatinib on neointimal hyperplasia in a balloon injury model of rat carotid arteries. Rats were orally administered with imatinib for 14 days after balloon injury, and sacrificed to analyze the neointimal formation. Intimal hyperplasia was inhibited by imatinib in a dose-dependent manner. Therefore imatinib presumably obstructed the growth of SMCs via interception on growth-signaling of PDGFR. The administration of imatinib after coronary stenting or the use of an imatinib-eluting stent may further reduce the risk of restenosis in patients.

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© 2008 Tohoku University Medical Press
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