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Basic and Clinical Research Regarding Gene Expression of Predictive Biomarkers derived from Circulating Inflammatory Cells in Acute Myocardial Ischemia

Research Project

Project/Area Number 17390232
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionKumamoto University

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)

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)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
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)
Keywordsacute coronary syndrome / microarray / scavenger receptor / macrophages / CCR2 / MMPs / reperfusion injury / cytokine / 再灌流傷害
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 .
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

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (25 results)

All 2007 2006 2005

All Journal Article (25 results)

  • [Journal Article] Targeted deletion of class A macrophage scavenger receptor increases the risk of cardiac rupture after experimental myocardial infarction.2007

    • Author(s)
      Tsujita K.
    • Journal Title

      Circulation. 115

      Pages: 1904-1911

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] CC chemokine receptor-2 deficiency attenuates oxidative stress and infarct size caused by myocardial ischemia-reperfusion in mice2006

    • Author(s)
      Hayasaki T
    • Journal Title

      Circulation Journal 70

      Pages: 342-351

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary 2005 Annual Research Report
  • [Journal Article] Reduced von Willebrand factor-cleaving protease (ADAMTS13) activity in acute myocardial infarction2006

    • Author(s)
      Kaikita K
    • Journal Title

      J Thromb Haemost. 11

      Pages: 2490-2493

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A -786T>C polymorphism in the endothelial nitric oxide synthase gene reduces serum nitrite/nitrate levels from the heart due to an intracoronary injection of acetylcholine.2006

    • Author(s)
      Nakayama M
    • Journal Title

      Pharmacogenetics and Genomics 16

      Pages: 339-345

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Elevated levels of remnant lipoproteins are associated with plasma platelet microparticles in patients with type-2 diabetes mellitus without obstructive coronary artery disease.2006

    • Author(s)
      Koga H
    • Journal Title

      European Heart Journal 27

      Pages: 817-823

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Plasma adiponectin levels are associated with coronary lesion complexity in men with coronary artery disease.2006

    • Author(s)
      Otsuka F
    • Journal Title

      Journal of the American College of Cardiology 48

      Pages: 1155-1162

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Effects of early statin treatment on symptomatic heart failure and ischemis events after acute myocardial infarction in Japanese.2006

    • Author(s)
      Sakamoto T
    • Journal Title

      American Journal of Cardiology 97

      Pages: 1165-1171

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] CC chemokine receptor-2 deficiency attenuates oxidative stress and infarct size caused by myocardial ischemia-reperfusion in mice.2006

    • Author(s)
      Hayasaki T.
    • Journal Title

      Circ J. 70

      Pages: 342-351

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Reduced von Willebrand factor-cleaving protease (ADAMTS13) activity in acute myocardial infarction.2006

    • Author(s)
      Kaikita K.
    • Journal Title

      J Thromb Haemost. 11

      Pages: 2490-2493

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] A-786T>C polymorphism in the endothelial nitric oxide synthase gene reduces serum nitrite/nitrate levels from the heart due to an intracoronary injection of acetylcholine.2006

    • Author(s)
      Nakayama M.
    • Journal Title

      Pharmacogenet Genomics. 16

      Pages: 339-345

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Elevated levels of remnant lipoproteins are associated with plasma platelet microparticles in patients with type-2 diabetes mellitus without obstructive coronary artery disease.2006

    • Author(s)
      Koga H.
    • Journal Title

      Eur Heart J. 27

      Pages: 817-823

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Plasma adiponectin levels are associated with coronary lesion complexity in men with coronary artery disease.2006

    • Author(s)
      Otsuka F.
    • Journal Title

      J Am Coll Cardiol. 48

      Pages: 1155-1162

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Effects of early statin treatment on symptomatic heart failure and ischemis events after acute myocardial infarction in Japanese.2006

    • Author(s)
      Sakamoto T.
    • Journal Title

      Am J Cardiol. 97

      Pages: 1165-1171

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Reduced von Willebrand factor-cleaving protease (ADAMTS13) activity acute myocardial infarction.2006

    • Author(s)
      Kaikita K
    • Journal Title

      J Thromb Haemost. 11

      Pages: 2490-2493

    • Related Report
      2006 Annual Research Report
  • [Journal Article] A - 786T>C polymorphism in the endothelial nitric oxide synthase gene reduces serum nitrite/nitrate levels from the heart due to an intracoronary injection of acetylcholine.2006

    • Author(s)
      Nakayama M
    • Journal Title

      Pharmacogenetics and Genomics 16

      Pages: 339-345

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Direct Effects of Aldosterone on Cardiomyocytes in the Presence of Normal and Elevated Extracellular Sodium.2006

    • Author(s)
      Yamamuro M
    • Journal Title

      Endocrinology 147

      Pages: 1314-1321

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Elevated Levels of VE-Cadherin-Positive Endothelial Microparticles in Patients WithType-2 Diabetes Mellitus and Coronary Artery Disease.2005

    • Author(s)
      Koga H.
    • Journal Title

      J Am Coll Cardiol. 45

      Pages: 1622-1630

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Stabilization of atheroma assessed by quantitative carotid ultrasound analysis of plaque vulnerability in non-hypercholesterolemic patients with coronary artery disease.2005

    • Author(s)
      Watanabe K.
    • Journal Title

      J Am Coll Cardiol. 46

      Pages: 2022-2030

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Id1 gene transfer confers angiogenic property on fully differentiated endothelial cells and contributes to therapeutic angiogenesis.2005

    • Author(s)
      Nishiyama K.
    • Journal Title

      Circulation. 112

      Pages: 2840-2850

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Direct Effects of Aldosterone on Cardiomyocytes in the Presence of Normal and Elevated Extracellular Sodium.2005

    • Author(s)
      Yamamuro M.
    • Journal Title

      Endocrinology. 147

      Pages: 1314-1321

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Usefulness of preprocedural platelet aggregation to predict restenosis after percutaneous coronary intervention2005

    • Author(s)
      Miyamoto S.
    • Journal Title

      Am J Cardiol. 96

      Pages: 71-73

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Elevated Levels of VE-Cadherin-Positive Endothelial Microparticles in Patients WithType-2 Diabetes Mellitus and Coronary Artery Disease.2005

    • Author(s)
      Koga H
    • Journal Title

      Journal of the American College of Cardiology 45

      Pages: 1622-1630

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Stabilization of atheroma assessed by quantitative carotid ultrasound analysis of plaque vulnerability in non-hypercholesterolemic patients with coronary artery disease.2005

    • Author(s)
      Watanabe K
    • Journal Title

      Journal of the American College of Cardiology 46

      Pages: 2022-2030

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Idl gene transfer confers angiogenic property on fully differentiated endothelial cells and contributes to therapeutic angiogenesis.2005

    • Author(s)
      Nishiyama K
    • Journal Title

      Circulation 112

      Pages: 2840-2850

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Usefulness of preprocedural platelet aggregation to predict restenosis after percutaneous coronary intervention.2005

    • Author(s)
      Miyamoto S
    • Journal Title

      The American Journal of Cardiology 96

      Pages: 71-73

    • Related Report
      2005 Annual Research Report

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Published: 2005-04-01   Modified: 2016-04-21  

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