CC Chemokine Receptor-2 Deficiency Attenuates Oxidative Stress and Infarct Size Caused by Myocardial Ischemia-Reperfusion in Mice
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概要
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Background Monocyte chemoattractant protein-1 (MCP-1) and its major receptor, CC chemokine receptor 2 (CCR2), have been shown to contribute to left ventricular remodeling after myocardial infarction. However, it is unknown whether CCR2 deficiency protects the myocardium after myocardial ischemia-reperfusion. The purpose of the present study was to investigate the effects of CCR2 deficiency on myocardial ischemia-reperfusion injury in mice. Methods and Results Experiments were performed in CCR2^<-/-> and wild-type mice subjected to 45min of ischemia followed by reperfusion. Macrophage infiltration in ischemic lesions was markedly reduced in CCR2^<-/-> mice compared with wild-type mice (p<0.01). The infarct size was significantly reduced in CCR2^<-/-> mice compared with wild-type mice at 3 days after reperfusion (p<0.001). In situ zymography revealed augmented gelatinolytic activity at 3 days after reperfusion in wild-type mice, but significantly less activity in CCR2^<-/-> mice. NADPH oxidase activity, the intensity of nitrotyrosine staining and expression of inducible nitric oxide synthase and thioredoxin-1 were significantly increased in ischemic myocardium in wild-type mice compared with CCR2^<-/-> mice, indicating a role for CCR2 in oxidative stress after ischemia-reperfusion. Conclusions Inhibition of the MCP-1/CCR2 pathway may be a useful strategy for attenuating myocardial ischemia-reperfusion injury.
- 社団法人日本循環器学会の論文
- 2006-02-20
著者
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Hayasaki Takanori
Division Of Cardiology Department Of Internal Medicine University Of Michigan Health System
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Takeya Motohiro
Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University
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Kuwahara Koichiro
京都大学 医学研究科内分泌代謝内科
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OGAWA Hisao
Cardiology Division, Department of Internal Medicine, National Cardiovascular Center
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OKUMA TOSHIYUKI
Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University
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Okuma Toshiyuki
Department Of Cell Pathology Graduate School Of Medical Sciences Kumamoto University
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Takeya Motohiro
Department Of Cell Pathology Graduate School Of Medical And Pharmaceutical Sciences Kumamoto Univers
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Hayasaki Takanori
Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University
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Kaikita Koichi
Cardiovascular Medicine, Graduate School of Medical Sciences, Graduate School of Medical Sciences, K
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Yamamoto Eiichiro
Cardiovascular Medicine, Graduate School of Medical Sciences, Kumamoto University
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Kuziel William
Autoimmune and Inflammatory Diseases, Protein Design Labs Inc
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Kuziel William
Autoimmune And Inflammatory Diseases Protein Design Labs Inc
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Yamamoto Eiichiro
Cardiovascular Medicine Graduate School Of Medical Sciences Kumamoto University
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