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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- Kitahara Masaki
- Shiraoka Research Station of Biological Science, Nissan Chemical Industries, Ltd.
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- Kanaki Tatsuro
- 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
書誌事項
- タイトル別名
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- NK-104 a Newly Developed HMG-CoA Reduct
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抄録
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.
収録刊行物
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- Jpn.J.Pharmacol.
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Jpn.J.Pharmacol. 77 (2), 117-128, 1998
公益社団法人 日本薬理学会
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詳細情報
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- CRID
- 1390001204286219776
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- NII論文ID
- 10008192883
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- NII書誌ID
- AA00691188
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- COI
- 1:CAS:528:DyaK1cXktFCisrc%3D
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- ISSN
- 13473506
- 00215198
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- NDL書誌ID
- 4514087
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- PubMed
- 9681568
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- Web Site
- https://ndlsearch.ndl.go.jp/books/R000000004-I4514087
- https://api.elsevier.com/content/article/PII:S0021519819311229?httpAccept=text/xml
- https://api.elsevier.com/content/article/PII:S0021519819311229?httpAccept=text/plain
- https://www.jstage.jst.go.jp/article/jjp/77/2/77_2_117/_pdf
- https://search.jamas.or.jp/link/ui/1998245175
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
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- PubMed
- CiNii Articles
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