A Matrix Metalloproteinase Inhibitor, ONO-4817, Suppresses the Development of Aortic Intimal Hyperplasia in Experimental Hyperlipidemic Rabbit
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概要
- 論文の詳細を見る
Inhibition of matrix metalloproteinases (MMPs) would be expected to suppress atherosclerotic neointimal proliferation and thus limit atheromatous plaque progression, but this has not yet been demonstrated morphologically in atherosclerotic intimal hyperplasia induced by cholesterol loading in experimental animals. We therefore investigated whether a broad-spectrum MMP inhibitor (MMPi), ONO-4817, could inhibit the development of intimal hyperplasia in male hyperlipidemic rabbits (n = 6) fed laboratory chow supplemented with 1% cholesterol for 2 months followed by a 1% cholesterol diet plus 100 mg/kg ONO-4817 for another month (Chol + ONO group). Control animals (n = 6) received no ONO-4817. When the aortas were studied both histologically and immunohistochemically, intimal hyperplasia was inhibited in Chol + ONO rabbits. The distribution of macrophages and MMP-12 in the hyperplastic tissue of the Chol + ONO rabbits was limited to the luminal side of the lesions. No such limitation in the distribution of macrophages and MMP-12 was observed in the control group. The distribution of smooth muscle cells in the hyperplastic tissue was not different between the Chol + ONO and control groups. However, the distribution of MMP-2 and MMP-12 was limited to the luminal side of lesions in the Chol + ONO group. This is the first reported evidence that an MMPi can suppress the development of intimal hyperplasia in hyperlipidemic rabbits.
- インターナショナル・ハート・ジャーナル刊行会の論文
著者
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Okamoto Yasuhiro
First Department Of Internal Medicine Self-defense Forces Central Hospital
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Nakamura Haruo
国立病院機構東京医療センター 循環器科
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Satomura Kimio
First Department of Internal Medicine, National Defense Medical College
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Nakayama Kazuhiro
First Department of Internal Medicine, National Defense Medical College
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Tanaka Nobukiyo
First Department of Internal Medicine, National Defense Medical College
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Ohsuzu Fumitaka
First Department of Internal Medicine, National Defense Medical College
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Imaki Junko
First Department of Anatomy, National Defense Medical College
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Yoshioka Masahiko
First Department of Anatomy, National Defense Medical College
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Ohsuzu Fumitaka
First Department Of Internal Medicine And The First Department Of Anatomy National Defense Medical C
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Okamoto Yasuhiro
First Department Of Internal Medicine And The First Department Of Anatomy National Defense Medical C
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Satomura Kimio
First Department Of Internal Medicine And The First Department Of Anatomy National Defense Medical C
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Yoshioka Masahiko
First Department Of Anatomy National Defense Medical College
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