NK-104, a Newly Developed HMG-CoA Reductase Inhibitor, Suppresses Neointimal Thickening by Inhibiting Smooth Muscle Cell Growth and Fibronectin Production in Balloon-Injured Rabbit Carotid Artery
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概要
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3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have been reported to suppress smooth muscle cell growth and arterial neointimal thickening. In this study, to elucidate the potency and mechanisms of NK-104 ((+)-monocalcium bis｛(3R, 5S, 6E)-7-[2-cyclopropyl-4-(4-fluorophenyl)-3-quinolyl]-3, 5-dihydroxy-6-heptenoate｝, CAS 147526-32-7) in neointimal thickening, the effect of NK-104 on the neointimal thickening, Br-dU-labeled cell number and extracellular matrix immunohistochemistry were examined in balloon-injured rabbit carotid artery. NK-104 suppressed the neointimal thickening dose-dependently, and the suppression was 69.5% at 1.0 mg/kg. NK-104 suppressed the intimal total and Br-dU-labeled cell number. Fibronectin and type I collagen were observed in 81% and 38% of the total intimal area in the control arteries, respectively, and the areas occupied by fibronectin and type I collagen were significantly decreased by 1.0 mg/kg NK-104 to 39% and 22%, respectively. The decrease in fibronectin per cell was more potently demonstrated. Aortic total and activated TGF-β contents that were markedly increased in the injured artery were increased further by NK-104. NK-104 concentration-dependently suppressed fibronectin content of the basement lesion in rabbit primary cultured smooth muscle cells. These findings suggest that NK-104 suppresses balloon-injury-induced neointimal thickening through inhibition of intimal smooth muscle cell growth and extracellular matrix accumulation.
- 社団法人 日本薬理学会の論文
- 1998-06-01
著者
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Kanaki Tatsuro
Shiraoka Research Station Of Biological Science Nissan Chemical Industries Ltd.
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KITAHARA Masaki
Shiraoka Research Station of Biological Science, Nissan Chemical Industries, Ltd.
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TOYODA Kyomi
Shiraoka Research Station of Biological Science, Nissan Chemical Industries, Ltd.
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MIYAKOSHI Chie
Shiraoka Research Station of Biological Science, Nissan Chemical Industries, Ltd.
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TANAKA Sakuya
Shiraoka Research Station of Biological Science, Nissan Chemical Industries, Ltd.
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TAMAKI Taro
Tokyo Research Laboratories, Pharmaceutical Division, Kowa Company, Ltd.
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SAITO Yasushi
The Second Department of Internal Medicine, School of Medicine, Chiba University
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Saito Yasushi
Department Of Clinical Cell Biology Chiba University Graduate School Of Medicine
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Tamaki Taro
Tokyo Research Laboratories Pharmaceutical Division Kowa Company Ltd.
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Toyoda Kyomi
Shiraoka Research Station Of Biological Science Nissan Chemical Industries Ltd.
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Tanaka Sakuya
Shiraoka Research Station Of Biological Science Nissan Chemical Industries Ltd.
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Miyakoshi Chie
Shiraoka Research Station Of Biological Science Nissan Chemical Industries Ltd.
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Tanaka S
Department Of Oral Physiology Hiroshima University School Of Dentistry
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Saito Yasushi
Department Of Clinical Endocrinology And Metabolism Chiba University Hospital
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Kitahara Masaki
Shiraoka Research Station Of Biological Science Nissan Chemical Industries Ltd.
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Saito Yasushi
The Second Department Of Internal Medicine Chiba University School Of Medicine
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Tanaka Shuji
Department of Oral Physiology, Hiroshima University School of Dentistry
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