title: Imatinib mesilate inhibits neointimal hyperplasia via growth inhibition of vascular smooth muscle cells in a rat model of balloon injury.
abstract: Restenosis is a major problem in percutaneous catheter intervention (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.
authors.affiliation: Division of Cardiology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
authors.forename: Yashiro
authors.initials: Y
authors.lastname: Makiyama
authors.forename: Ken
authors.initials: K
authors.lastname: Toba
authors.forename: Kiminori
authors.initials: K
authors.lastname: Kato
authors.forename: Satoru
authors.initials: S
authors.lastname: Hirono
authors.forename: Takuya
authors.initials: T
authors.lastname: Ozawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Saigawa
authors.forename: Shiro
authors.initials: S
authors.lastname: Minagawa
authors.forename: Manabu
authors.initials: M
authors.lastname: Isoda
authors.forename: Fuyuki
authors.initials: F
authors.lastname: Asami
authors.forename: Noboru
authors.initials: N
authors.lastname: Ikarashi
authors.forename: Masato
authors.initials: M
authors.lastname: Oda
authors.forename: Masato
authors.initials: M
authors.lastname: Moriyama
authors.forename: Masutaka
authors.initials: M
authors.lastname: Higashimura
authors.forename: Toshiki
authors.initials: T
authors.lastname: Kitajima
authors.forename: Keita
authors.initials: K
authors.lastname: Otaki
authors.forename: Yoshifusa
authors.initials: Y
authors.lastname: Aizawa
mesh_terms: D000818:Animals; D001549:Benzamides; D002404:Catheterization / Q000009:adverse effects*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006965:Hyperplasia / Q000139:chemically induced / Q000517:prevention & control; D000068877:Imatinib Mesylate; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000473:pathology*; D010879:Piperazines / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology; D017540:Tunica Media / Q000187:drug effects / Q000473:pathology
chemical_list: D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate