Distribution Profiles of Membrane Type-1 Matrix Metalloproteinase (MT1-MMP), Matrix Metalloproteinase-2 (MMP-2) and Cyclooxygenase-2 (COX-2) in Rabbit Atherosclerosis : Comparison with Plaque Instability Analysis(Analytical Biochemistry)
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概要
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Background: Despite increasing evidence that membrane type 1 matrix metalloproteinase (MT1-MMP), matrix metalloproteinase-2 (MMP-2), and cyclooxygenase-2 (COX-2) are involved in the pathogenesis of atherosclerosis, the possible links among these enzymes remain unclear. Accordingly, we investigated the distribution of MT1-MMP, MMP-2, and COX-2 immunohistologically in the atherosclerotic lesions of hypercholesterolemic (WHHLMI) rabbits. Methods and Results: Distribution of MT1-MMP, MMP-2, and COX-2 was examined by immunohistochemical staining using sixty cross sections of the ascending-arch and thoracic aortas prepared from 4 WHHLMI rabbits. MT1-MMP and MMP-2 staining was prominently observed in the macrophage-rich regions of the atheromatous lesions, and was positively correlated with morphological vulnerability (r=0.63 for MT1-MMP; r=0.60 for MMP-2; p<0.0001). MT1-MMP staining was positively correlated with MMP-2 staining (r=0.61,p<0.0001). COX-2 staining was also the highest in the macrophage-rich regions of the atheromatous lesions, with relatively high staining levels in other more stable lesions. Conclusions: Co-distribution of MT1-MMP, MMP-2, and COX-2 was demonstrated in grade IV atheroma, indicating a possible link among these enzymes in the destabilization of atherosclerotic plaques. The relatively high COX-2 distribution in other more stable lesions may indicate its additional roles in the stabilization of atherosclerotic lesions. The present findings in hypercholesterolemic rabbits should help advance our understanding of the pathophysiology of atherosclerosis and provide useful information for the development of new therapeutic and diagnostic (imaging) agents that target MMPs and COX-2 in atherosclerosis.
- 社団法人日本薬学会の論文
- 2007-09-01
著者
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Saji H
Graduate School Of Pharmaceutical Sciences Kyoto University
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Saji Hideo
明治鍼灸大学
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Saji Hideo
Department Of Patho-functional Bioanalysis Graduate School Of Pharmaceutical Sciences Kyoto Universi
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Saji Hideo
茨城県立医療大学 放射線技術科学
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Shiomi Masashi
Institute for experimental animals, Kobe University School of Medicine
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Shiomi Masashi
Institute For Experimental Animals Kobe University School Of Medicine
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Shiomi Masashi
京都大学 薬学研究科病態機能分析学
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Kitamura Youji
Department Of Pharmaceutical Sciences Graduate School Of Medicine And Dentistry And Pharmaceutical S
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Temma Takashi
Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto Univer
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Kuge Yuji
Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto Univer
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Takai Nozomi
Department of Patho-Functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto Univer
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ISHINO Seigo
Department of Patho-functional Bioanalysis, Graduate School of Pharmaceutical Sciences, Kyoto Univer
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Ishino Seigo
Department Of Patho-functional Bioanalysis Graduate School Of Pharmaceutical Sciences Kyoto Universi
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Takai Nozomi
Department Of Patho-functional Bioanalysis Graduate School Of Pharmaceutical Sciences Kyoto Universi
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Shiomi Masashi
Institute For Experimental Animals Kobe University Graduate School Of Medicine
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Sakahara H
Department Of Radiology Hamamatsu University School Of Medicine
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Saji Hideo
Dep. Of Patho-functional Bioanalysis Graduate School Of Pharmaceutical Sciences Kyoto Univ.
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Kuge Yuji
Department Of Tracer Kinetics Hokkaido University School Of Medicine
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Kuge Yuji
Department Of Patho-functional Bioanalysis Graduate School Of Pharmaceutical Sciences Kyoto Universi
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Kuge Yuji
Department Of Nuclear Medicine Graduate School Of Medicine Hokkaido University
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Kitamura Youji
Department Of Patho-functional Bioanalysis Graduate School Of Pharmaceutical Sciences Kyoto Universi
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Sakahara H
Kyoto Univ. School Of Medicine
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Shiraishi Hirokazu
Graduate School Of Pharmaceutical Sciences Kyoto University
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Saji Hideo
Department Of Cardiology Matsushita Memorial Hosipital
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Temma Takashi
Department Of Patho-functional Bioanalysis Graduate School Of Pharmaceutical Sciences Kyoto University
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