Imatinib Mesilate Inhibits Neointimal Hyperplasia via Growth Inhibition of Vascular Smooth Muscle Cells in a Rat Model of Balloon Injury
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- Makiyama Yashiro
- Division of Cardiology, Niigata University Graduate School of Medical and Dental Sciences
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- Toba Ken
- Division of Hematology, Niigata University Graduate School of Medical and Dental Sciences
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- Kato Kiminori
- Division of Cardiology, Niigata University Graduate School of Medical and Dental Sciences
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- Hirono Satoru
- Division of Cardiology, Niigata University Graduate School of Medical and Dental Sciences
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- Ozawa Takuya
- Division of Cardiology, Niigata University Graduate School of Medical and Dental Sciences
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- Saigawa Takashi
- Division of Cardiology, Niigata University Graduate School of Medical and Dental Sciences
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- Minagawa Shiro
- Division of Cardiology, Niigata University Graduate School of Medical and Dental Sciences
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- Isoda Manabu
- Division of Cardiovascular Surgery, Niigata University Graduate School of Medical and Dental Sciences
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- Asami Fuyuki
- Division of Cardiovascular Surgery, Niigata University Graduate School of Medical and Dental Sciences
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- Ikarashi Noboru
- Division of Cardiology, Niigata University Graduate School of Medical and Dental Sciences
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- Oda Masato
- Division of Cardiology, Niigata University Graduate School of Medical and Dental Sciences
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- Moriyama Masato
- Division of Hematology, Niigata University Graduate School of Medical and Dental Sciences
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- Higashimura Masutaka
- Division of Hematology, Niigata University Graduate School of Medical and Dental Sciences
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- Kitajima Toshiki
- Division of Hematology, Niigata University Graduate School of Medical and Dental Sciences
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- Otaki Keita
- Division of Cardiology, Niigata University Graduate School of Medical and Dental Sciences
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- Aizawa Yoshifusa
- Division of Cardiology, Niigata University Graduate School of Medical and Dental Sciences
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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.
Journal
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- The Tohoku Journal of Experimental Medicine
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The Tohoku Journal of Experimental Medicine 215 (4), 299-306, 2008
Tohoku University Medical Press
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Details 詳細情報について
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- CRID
- 1390282679217671424
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- NII Article ID
- 130004459709
- 10021951207
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- NII Book ID
- AA00863920
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- ISSN
- 13493329
- 00408727
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- Text Lang
- en
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- Data Source
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- JaLC
- Crossref
- CiNii Articles
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- Abstract License Flag
- Disallowed