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Role of endothelial cell selective adhesion molecule (ESAM) in the genesis of diabetic vasculopathy

Research Project

Project/Area Number 17590734
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

ISHIDA Tatsuro  Kobe University, Graduate School of Medicine, Assistant Professor, 大学院・医学系研究科, 助手 (00379413)

Co-Investigator(Kenkyū-buntansha) YOKOYAMA Mitsuhiro  Kobe University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (40135794)
HIRATA Ken-ichi  Kobe University, Graduate School of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (20283880)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2005: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywordsadhesion molecule / diabetes mellitus / endothelium / retinopathy / angiogenesis / atherosclerosis / diabetic vasculopathy / inlammation
Research Abstract

1) Role of ESAM in diabetes mellitus
Endothelial cell selective adhesion molecule (ESAM) is a new member of the immunoglobulin family adhesion molecule which has been cloned from vascular endothelial cells. ESAM expression is selectively restricted to vascular endothelial cells. To clarify the role of ESAM in the genesis of diabetic vasculopathy, aortic endothelial cells were isolated from wild-type and ESAM knockout mice and endothelial permeability was evaluated using the modified Boyden chamber system with the Evance Blue dye. The ESAM deficient endothelial cells showed a significant increase of endothelial cell permeability when compared to wild type endothelial cells. Consistent with this result, ESAM knockout mice showed marked albuminuria when compared to wild type mice. When wild type and ESAM knockout mice were injected with streptozotocin to evoke diabetes, ESAM knockout mice showed severer albuminuria and hypoalbuminemia. These results indicate that ESAM regulates endothelial permeability, and a decrease in ESAM expression increase the albuminuria. Thus, ESAM may play an important role in the pathophysiology of early stages of diabetic nephropathy by modulating glomerular permeability.
2) Role of ESAM in atherosclerosis
ESAM knockout mice were bred with apoE knockout mice to generate the ESAM-apoE double knockout mice. Aortic atherosclerotic lesions were evaluated by Sudan III staining. Atherosclerotic lesion of ESAM-apoE double knockout mice were significantly smaller than the control apoE knockout mice. The macrophage content in the atherosclerotic lesion was smaller in ESAM-apoE double knockout mice than in apoE knockout mice. These results indicate that ESAM regulates the formation of atherosclerosis by modulating eodnthelial-hepatopoietic cell interaction.

Report

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

    (27 results)

All 2007 2006 2005 Other

All Journal Article (27 results)

  • [Journal Article] Endothelial lipase is increased by inflammation andpromotes LDL uptake in macrophages2007

    • Author(s)
      Yasuda, et al.
    • Journal Title

      J Atheroscl Thromb Circ J (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Endothelial nitric oxide synthase uncoupling : Is it a physiological mechanism of endothelium-dependent relaxation in cerebral artery?2007

    • Author(s)
      Yokoyama M, et al.
    • Journal Title

      Cardiovasc Res 73

      Pages: 8-9

    • 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] Neointimal coverage of sirolimus-eluting stents at 6-month follow-up : evaluated by optical coherence tomography.2007

    • Author(s)
      Matsumoto D, et al.
    • Journal Title

      Eur Heart J 28

      Pages: 961-967

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Endothelial nitric oxide synthase uncoupling : Is it a physiological mechanism of endothelium-dependent relaxation in cerebral artery?2007

    • Author(s)
      Yokoyama M, et al.
    • Journal Title

      Cardiovasc Res. 73(1)

      Pages: 8-9

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Angiopoietin-like protein3 regulates plasma HDL cholesterol through suppression of endothelial lipase.2006

    • Author(s)
      Simamura M, et al.
    • Journal Title

      Arterioscler Thromb Vasc Biol 27

      Pages: 366-372

    • 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] Ventilator-induced lung injury is reduced in transgenic mice that overexpress endothelial nitric oxide synthase.2006

    • Author(s)
      Takenaka K, et al.
    • Journal Title

      Am J Physiol Lung Cell Mol Physiol. 290

    • 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] Endothelial urocortin has potent antioxidative properties and upregulated by inflammatory cytokines and pitavastatin.2006

    • Author(s)
      Honjo T, et al.
    • Journal Title

      J Vasc Res 43・2

      Pages: 131-138

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Toll-like receptor 4 expressions on peripheral blood monocytes were enhanced in coronary artery disease even in patients with low C-reactive protein.2006

    • Author(s)
      Shiraki R, et al.
    • Journal Title

      Life Sci. 80(1)

      Pages: 59-66

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Angiotensin II type 1 receptor blocker telmisartan suppresses superoxide production and reduces atherosclerotic lesion formation in apolipoprotein E-deficient mice.2006

    • Author(s)
      Takaya T, et al.
    • Journal Title

      Atherosclerosis. 186(2)

      Pages: 402-410

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Angiopoietin-like protein3 regulates plasma HDL cholesterol through suppression of endothelial lipase.2006

    • Author(s)
      Shimamura M, et al.
    • Journal Title

      Arterioscler Thromb Vasc Biol. 27(2)

      Pages: 366-72

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Chylomicron remnants upregulate CD40 expression via the ERK pathway and a redox-sensitive mechanism in THP-1 cells.2006

    • Author(s)
      Kamemura K, et al.
    • Journal Title

      Atherosclerosis. 187(2)

      Pages: 257-6

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Endothelial urocortin has potent antioxidative properties and is upregulated by inflammatory cytokines and pitavastatin.2006

    • Author(s)
      Honjo T, et al.
    • Journal Title

      J Vasc Res. 43(2)

      Pages: 131-8

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Chylomicron remnants upregulate CD40 expression via the ERK pathway and a redox-sensitive mechanism in THP-1 cells.2006

    • Author(s)
      Kamemura K, et al.
    • Journal Title

      Atherosclerosis 187

      Pages: 257-264

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Endothelial urocortin has potent antioxidative properties and is upregulated by inflammatory cytokines and pitavastatin.2006

    • Author(s)
      Honjo T, et al.
    • Journal Title

      J Vasc Res 43・2

      Pages: 131-138

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Chylomicron remnants upregulate CD40 expression via the ERK pathway and a redox-sensitive mechanism in THP-1 cells.2006

    • Author(s)
      Kamemura K
    • Journal Title

      Atherosclerosis (in press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Endothelial urocortin has potent antioxidative properties and is upregulated by inflammatory cytokines and pitavastatin.2006

    • Author(s)
      Honjo T
    • Journal Title

      J Vasc Res 43・2

      Pages: 131-138

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Endothelial lipase gene polymorphism is associated with acute myocardial infarction independent of high-density lipoprotein cholesterol levels2005

    • Author(s)
      Shimizu M, et al.
    • Journal Title

      Cardiovasc Res. 66(3)

      Pages: 594-600

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Possible role of brain-derived neurotrophic factor in the pathogenesis of coronary artery disease.2005

    • Author(s)
      Ejiri J, et al.
    • Journal Title

      Circulation. 112(14)

      Pages: 2114-2120

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] New function of calreticulin : calreticulin-dependent mRNA destabilization.2005

    • Author(s)
      Yokoyama M, et al.
    • Journal Title

      Circ Res. 97(10)

      Pages: 961-963

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Xenogenic smooth muscle cell immunization reduces neointimal formation in balloon-injured rabbit carotid arteries.2005

    • Author(s)
      Shinohara M, et al.
    • Journal Title

      Cardiovasc Res. 68(2)

      Pages: 249-258

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Increased expression of endothelial lipase in rat models of hypertension.2005

    • Author(s)
      Shimokawa Y, et al.
    • Journal Title

      Cardiovasc Res. 66(3)

      Pages: 594-600

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] New function of calreticulin : calreticulin-dependent mRNA destabilization.2005

    • Author(s)
      Yokoyama M
    • Journal Title

      Circ Res 11・97

      Pages: 961-963

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Xenogenic smooth muscle cell immunization reduces neointimal formation in balloon-injured rabbit carotid arteries.2005

    • Author(s)
      Shinohara M
    • Journal Title

      Cardiovasc Res 68・2

      Pages: 249-258

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Possible role of brain-derived neurotrophic factor in the pathogenesis of coronary artery disease.2005

    • Author(s)
      Ejiri J
    • Journal Title

      Circulation 112・14

      Pages: 2114-2120

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Increased expression of endothelial lipase in rat model of hypertension.2005

    • Author(s)
      Shimokawa Y
    • Journal Title

      Cardiovasc Res 66・3

      Pages: 594-600

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Neointimal coverage of sirolimus-eluting stents at 6-month follow-up : evaluated by optical coherence tomography.

    • Author(s)
      Matsumoto D, et al.
    • Journal Title

      Eur Heart J. (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Neointimal coverage of sirolimus-eluting stents at 6-month follow-up : evaluated by optical coherence tomography.

    • Author(s)
      Matsumoto D, et al.
    • Journal Title

      Eur Heart J (In press)

    • Related Report
      2006 Annual Research Report

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

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