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Physiological function of apolipoprotein J in neointimal hyperplasia after vascular injury and atherosclerosis : Mechanism and application to treatment

Research Project

Project/Area Number 16590701
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

MIYATA Masaaki  Kagoshima University, University Hospital Faculty of Medicine and Dentistry, Research Associate, 医学部・歯学部附属病院, 助手 (00347113)

Co-Investigator(Kenkyū-buntansha) TEI Chuwa  Kagoshima University, Graduate School of Medical and Dental Sciences, Professor, 大学院・医歯学総合研究科, 教授 (10163891)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2005: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
Keywordsatherosclerosis / vascular remodeling / apolipoprotein J / restenosis / knockout mouse / transgenic mouse
Research Abstract

Neointimal hyperplasia is a major cause of restenosis after coronary intervention. We reported that apolipoprotein J/clusterin (apoJ) was dramatically induced in media and neointima after vascular injury, and expression of clusterin stimulated proliferation and migration of cultured vascular smooth muscle cell (SMC).
First, we investigated the physiological function of apoJ in neointimal hyperplasia after vascular injury. We used 3 different types of mice as follows ; apoJ transgenic mice overexpressing apoJ in vessel-selective manner (apoJ-Tg), apoJ deficient mice (apoJ-KO), and wild C57BL6 mice. A non-restrictive cuff was placed around the femoral artery of each male mouse, and all mice were sacrificed 4 weeks later for the planimetric measurements of neointimal and medial area. The apoJ-Tg mice showed a significant increase of neointimal hyperplasia, and apoJ-KO mice showed a significant decrease of neointimal hyperplasia as compared with wild mice. In order to analyze the mechanism … More of promoting effect of apoJ on neointimal thickening after vascular injury, we performed immunohistochemical staining using antibodies against caspase-3, p53 and p27. The immunoreactivity for caspase-3 in neointima demonstrated no differences among 3 types of mice. However, apoJ-KO mice showed the increased immunoreactivities for both p53 and p27 in neointimal SMC as compared with apoJ-Tg and wild mice. These result suggest that apoJ deficiency may decrease neointimal hyperplasia by G1 arest of SMC.
Second, we investigated the physiological function of apoJ in atherosclerosis using apoJ-KO and apolipoprotein E-deficient mice (apoE-KO). ApoJ-KO was crossbred with apoE-KO, and double knockout mice (apoJ-KO/apoE-KO) was established. Mice were fed a chew diet and analyzed at 25 weeks of age. Atherosclerotic lesions in the aortic root were measured by a quantitative assay. The atherosclerotic lesion of apoJ-KO/apoE-KO mice were significantly smaller than that of apoE-KO. In order to analyze the mechanism of promoting effect of apoJ on atherosclerosis, we performed immunohistochemical staining using antibodies against NF-kB and B-MYB. The immunoreactivity for NF-kB and B-MYB in nuclei of smooth muscle cells in atherosclerotic lesions of apoJ-KO/apoE-KO was decresed compared to that of apoE-KO. ApoJ-deficiency decreased atherosclerosis via inhibition of NF-kB and B-MYB in apolipoprotein E-deficient mice, suggesting that apoJ is an atherogenic factor.
Inhibition of apoJ expression may provide a novel therapy to limit restenosis after coronary intervention or atherosclerosis. Less

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (14 results)

All 2006 2005 2004

All Journal Article (12 results) Book (2 results)

  • [Journal Article] Expression of lectin-like oxidized LDL receptor-1 in smooth muscle cells after vascular injury2006

    • Author(s)
      Eto H, Miyata M, et al.
    • Journal Title

      Biochemical and Biophysical Research Communications 341・2

      Pages: 591-598

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Repeated Thermal Therapy Up-Regulates Endotherial Nitric Oxide Synthase and Augments Angiogenesis in a Mouse Model Hindlimb Ischemia2006

    • Author(s)
      Akasaki Y, Miyata M, et al.
    • Journal Title

      Circulation Journal 70・4

      Pages: 463-470

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Expression of lectin-like oxidized LDL receptor-1 in smooth muscle cells after vascular injury.2006

    • Author(s)
      Eto H, Miyata M, Kume N, Minami M, Itabe H, Orihara K, Hamasaki S, Biro S, Otsuji Y, Kita T, Tei C.
    • Journal Title

      Biochemical and Biophysical Research Communications. 341(2)

      Pages: 591-598

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Repeated thermal therapy up-regulates endothelial nitric oxide synthase and augments angiogenesis in a mouse model of hindlimb ischemia.2006

    • Author(s)
      Akasaki Y, Miyata M, Eto H, Shirasawa T, Hamada N, Ikeda Y, Biro S, Otsuji Y, Tei C.
    • Journal Title

      Circ J. 70(4)

      Pages: 463-470

    • NAID

      110004497236

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Repeated Thermal Therapy Up-Regulates Endotherial Nitric Oxide Synthase and Augments Angiogenesis in a Mouse Model of Hindlimb Ischemia2006

    • Author(s)
      Akasaki Y, Miyata M, et al.
    • Journal Title

      Circulation Journal 70・4

      Pages: 463-470

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 再狭窄の分子機構2005

    • Author(s)
      宮田昌明, 鄭 忠和
    • Journal Title

      Molecular Medicine 42

      Pages: 372-376

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Molecular mechanism of restenosis.2005

    • Author(s)
      Miyata M, Tei C.
    • Journal Title

      Molecular Medicine. 42

      Pages: 372-376

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Repeated sauna therapy reduces urinary 8-epi-prostaglandin F2_α2004

    • Author(s)
      Masuda A, Miyata M, et al.
    • Journal Title

      Jpn Heart J 45・2

      Pages: 297-303

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Effects of repeated sauna treatment on ventricular arrhythmias in patients with chronic heart failure2004

    • Author(s)
      Kihara T, Biro S, et al.
    • Journal Title

      Circulation Journal 68・12

      Pages: 1146-1151

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] Repeated sauna therapy reduces urinary 8-epi-prostaglandin F2_α.2004

    • Author(s)
      Masuda A, Miyata M, Kihara T, Minagoe S, Tei C.
    • Journal Title

      Jpn Heart J. 45

      Pages: 297-303

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Effects of repeated sauna treatment on ventricular arrhythmias in patients with chronic heart failure.2004

    • Author(s)
      Kihara T, Biro S, Ikeda Y, Fukudome T, Shinsato T, Masuda A, Miyata M, Hamasaki S, Otsuji Y, Minagoe S, Akiba S, Tei C.
    • Journal Title

      Circ J. 68

      Pages: 1146-1151

    • NAID

      110002696005

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Repeated sauna therapy reduces urinary 8-epi-prostaglandin F2 α2004

    • Author(s)
      Masuda A, Miyata M, et al.
    • Journal Title

      Jpn Heart J 45

      Pages: 297-303

    • Related Report
      2004 Annual Research Report
  • [Book] DATA UPDATE 循環器系 第3版 WISE(Women's Ischemia Syndrome Evaluation)(山口 徹, 日和田邦男, 斎藤 康 編)2004

    • Author(s)
      宮田昌明, 鄭 忠和
    • Total Pages
      401
    • Publisher
      先端医学社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] DATA UPDATE 循環器系 第3版 WISE (Women's Ischemia Syndrome Evaluation)2004

    • Author(s)
      宮田昌明, 鄭 忠和
    • Total Pages
      401
    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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