Tohoku J. Exp. Med., 2008, 215(4)

Imatinib Mesilate Inhibits Neointimal Hyperplasia via Growth Inhibition of Vascular Smooth Muscle Cells in a Rat Model of Balloon Injury

YASHIRO MAKIYAMA,¹ KEN TOBA,² KIMINORI KATO,¹ SATORU HIRONO,¹ TAKUYA OZAWA,¹ TAKASHI SAIGAWA,¹ SHIRO MINAGAWA,¹ MANABU ISODA,³ FUYUKI ASAMI,³ NOBORU IKARASHI,¹ MASATO ODA,¹ MASATO MORIYAMA,² MASUTAKA HIGASHIMURA,² TOSHIKI KITAJIMA,² KEITA OTAKI¹ and YOSHIFUSA AIZAWA¹

¹Division of Cardiology, Niigata University Graduate School of Medical and Dental Sciences
²Division of Hematology, Niigata University Graduate School of Medical and Dental Sciences
³Division of Cardiovascular Surgery, Niigata University Graduate School of Medical and Dental Sciences

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.

keywords —— coronary intervention; intimal hyperplasia; restenosis; imatinib mesilate; coxsackievirus and adenovirus receptor.

© 2008 Tohoku University Medical Press

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Tohoku J. Exp. Med., 2008, 215, 299-306

Correspondence: Kiminori Kato, The First Department of Internal Medicine, Niigata University Medical and Dental Hospital, 1-754 Asahimachi-dori, Niigata 951-8510, Japan.