| Project/Area Number |
17390232
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Kumamoto University |
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Principal Investigator |
OGAWA Hisao Kumamoto University, Graduate School of Medical Sciences, Department of Cardiovascular Medicine, Professor, 大学院医学薬学研究部, 教授 (50177135)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIMURA Michihiro Kumamoto University, Graduate School of Medical Sciences, Department of Cardiovascular Medicine, Associate Professor, 大学院医学薬学研究部, 助教授 (30264295)
SUGIYAMA Seigo Kumamoto University, Hospital, Department of Cardiovascular Medicine, Assistant Professor, 医学部附属病院, 講師 (90274711)
KAWANO Hiroaki Kumamoto University, Graduate School of Medical Sciences, Department of Cardiovascular Medicine, Associate Professor, 大学院医学薬学研究部, 助教授 (10305013)
KAIKITA Koichi Kumamoto University, Graduate School of Medical Sciences, Department of Cardiovascular Medicine, Assistant Professor, 大学院医学薬学研究部, 講師 (30346978)
NAKAYAMA Masafumi Kumamoto University, Graduate School of Medical Sciences, Department of Cardiovascular Medicine, Assistant Professor, 大学院医学薬学研究部, 助手 (30346986)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥14,800,000 (Direct Cost: ¥14,800,000)
Fiscal Year 2006: ¥6,700,000 (Direct Cost: ¥6,700,000)
Fiscal Year 2005: ¥8,100,000 (Direct Cost: ¥8,100,000)
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| Keywords | acute coronary syndrome / microarray / scavenger receptor / macrophages / CCR2 / MMPs / reperfusion injury / cytokine / 再灌流傷害 |
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| Research Abstract |
In the gene chip microarray analysis, we focused on Class A macrophage scavenger receptor (SR-A), which was the most strongly increased factor in the acute phase than in the chronic phase among the immune response factors according to the gene ontologic analysis. The SR-A mRNA levels of the peripheral circulating mononuclear cells were highest in the patients with acute coronary syndrome (p<0.01), while there was no significant difference between the control and the stable angina groups. The mRNA levels of SR-A in the coronary atheroscrelotic lesions obtained from directional coronary atherectomy were significantly higher in the patients with unstable angina than in the patients with stable angina (p<0.03). Furthermore, we examined the relationship between SR-A expression and prognosis in 73 patients with ischemic heart disease. Kaplan-Meier analysis demonstrated that patients with high SR-A mRNA levels had a significantly higher probability for the development of cardiovascular events
… More
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Next, we investigated the effects of CCR2 deficiency on myocardial ischemia-reperfusion injury in mice. Experiments were performed in CCR2^<-/-> and wild-type mice subjected to 45 minutes of ischemia followed by reperfusion. Macrophage infiltration in ischemic lesion was gradually increased and peaked at 3 days after reperfusion in wild-type nice. However, this process was markedly reduced in CCR2^<-1-> mice (P<0.01). 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^<-1-> 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. Less
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