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2005 Fiscal Year Annual Research Report

"タンパク質"修飾酸化LDLの診断法の確立と動脈硬化における意義に関する研究

Research Project

Project/Area Number 16659141
Research InstitutionOkayama University

Principal Investigator

松浦 栄次  岡山大学, 大学院医歯薬学総合研究科, 助教授 (20181688)

Co-Investigator(Kenkyū-buntansha) 四方 賢一  岡山大学, 医学部・歯学部附属病院, 講師 (00243452)
稲垣 純子  岡山大学, 大学院医歯薬学総合研究科, 助手 (90271056)
Keywords酸化LDL / β2-グリコプロテインI(β2GPI) / C-反応性タンパク質(CRP) / 動脈硬化 / 感染免疫 / 抗リン脂質抗体症候群(APS) / 脂質代謝異常 / 複合体
Research Abstract

酸化ストレスが原因となる生活習慣病が我が国でも増加の一途を辿っている。この状況の中、動脈硬化や冠動脈疾患の早期診断、治療中の経過観察に有益な診断法として、酸化LDLや高感度C-反応性タンパク質(CRP)の測定法が開発されてきた。しかしながら、CRPおよびβ_2-グリコプロテインI(β_2GPI)が酸化LDLと複合体を形成していることが明らかになったため、早期に、これらタンパク質修飾LDLの臨床意義を明らかにし、それらの診断法を確立する必要があると考えた。そこで、平成16年度からの2年間の本萌芽研究で、基礎・臨床分野に跨る解析を体系的に行い、タンパク質修飾酸化LDLの動脈硬化への関わりについて検証すると共に、臨床診断薬としてのELISAによる修飾酸化LDLの測定法を確立することを計画した。
今年度は、抗β_2GPI抗体、抗CRP抗体などを用いたCRP/β_2GPI修飾酸化LDLのELISA法を確立し、糖尿病、虚血性心疾患、脳血管障害、閉塞性動脈硬化症、慢性腎疾患等の動脈硬化性疾患、および膠原病(特に、SLE、APS)を対象に、古典的な動脈硬化の指標とCRP/β_2GPI修飾酸化LDLとの関連性について検討を行った。CRP/酸化LDL/β_2GPI複合体は、動脈硬化性疾患である糖尿病患者血中、特に、IMTで診断される動脈硬化陽性の患者で特異的に検出された。一方、急性炎症性(熱発性)疾患で、CRP陽性の患者では全く検出されなかった。高感度CRPと高い相関を示すため、冠動脈疾患の危険因子と考えられている高感度CRPの本体が本複合体であると考えられる。動脈硬化を有する患者の頸動脈(動脈硬化巣)にCRP、酸化LDL、β_2GPIの局在が認められたことより、これらの複合体は動脈硬化巣で形成され末梢血流中へ逸脱すると考えられた。

  • Research Products

    (24 results)

All 2006 2005

All Journal Article (20 results) Book (4 results)

  • [Journal Article] Oxidized low-density lipoprotein and β2-glycoprotein I in patients with systemic lupus erythematosus and increased carotid intima-media thickness : implications in autoimmune-mediated atherosclerosis.2006

    • Author(s)
      Lopez, LR
    • Journal Title

      Lupus 15・2

      Pages: 80-86

  • [Journal Article] Roles of interaction between β2-glycoprotein I and plasma lipoproteins in atherosclerosis.2006

    • Author(s)
      Matsuura, E
    • Journal Title

      Prog Lipid Res (in press)

  • [Journal Article] Atherogenic oxidized low-density lipoprotein/β2-glycoprotein I (oxLDL/β2GPI) complexes in patients with systemic lupus erythematosus and antiphospholipid syndrome.2006

    • Author(s)
      Matsuura, E
    • Journal Title

      Lupus (in press)

  • [Journal Article] Antibodies against β2-glycoprotein I complexed with an oxidized lipoprotein relate to intima thickening of carotid arteries in primary antiphospholipid syndrome.2006

    • Author(s)
      Ames, PRJ
    • Journal Title

      Clin Dev Immunol (in press)

  • [Journal Article] Significance of valine/leucine^<247> polymorphism of β2-glycoprotein I in antiphospholipid syndrome : increased reactivity of anti-β2-glycoprotein I autoantibodies to the valine^<247> β2-glycoprotein I variant.2005

    • Author(s)
      Yasuda, S
    • Journal Title

      Arthritis Rheum 52・1

      Pages: 212-218

  • [Journal Article] Characterization of a murine anti-laminin-1 monoclonal antibody (AK8) produced by immunization with mouse-derived laminin-1.2005

    • Author(s)
      Kondo, A
    • Journal Title

      Clin Dev Immunol 12・1

      Pages: 67-73

  • [Journal Article] From animal models to human genetics : research on the induction and pathogenicity of autoantibodies.2005

    • Author(s)
      Conrad, K
    • Journal Title

      Autoimmun Rev 4・3

      Pages: 178-187

  • [Journal Article] Binding of β2-glycoprotein I to anionic phospholipids facilitates processing and presentation of a cryptic epitope that activates pathogenic autoreactive T cells.2005

    • Author(s)
      Kuwana, M
    • Journal Title

      Blood 105・4

      Pages: 1552-1557

  • [Journal Article] Oxidized low-density lipoprotein/β2-glycoprotein I complexes and autoantibodies in patients with type 2 diabetes mellitus.2005

    • Author(s)
      Lopez, LR
    • Journal Title

      Ann NY Acad Sci 1051

      Pages: 97-103

  • [Journal Article] Pregnancy loss and endometriosis : pathogenic role of anti-laminin-1 autoantibodies.2005

    • Author(s)
      Inagaki, J
    • Journal Title

      Ann NY Acad Sci 1051

      Pages: 174-184

  • [Journal Article] OxLDL/β2GPI complexes and autoantibodies in patients with systemic lupus erythematosus, systemic sclerosis and antiphospholipid syndrome : pathogenic Implications for vascular involvement.2005

    • Author(s)
      Lopez, LR
    • Journal Title

      Ann NY Acad Sci 1051

      Pages: 313-322

  • [Journal Article] The role of innate and adaptive immunity to oxidized low-density lipoprotein in the development of atherosclerosis.2005

    • Author(s)
      Kobayashi, K
    • Journal Title

      Ann NY Acad Sci 1051

      Pages: 422-454

  • [Journal Article] Chemical xenobiotics and mitochondrial autoantigens in primary biliary cirrhosis : identification of antibodies against a common environmental, cosmetic, and food additive, 2-octynoic acid.2005

    • Author(s)
      Amano, K
    • Journal Title

      J Immunol 174・9

      Pages: 5874-5883

  • [Journal Article] Oxidized LDL/β2-glycoprotein I complex : new aspects in atherosclerosis.2005

    • Author(s)
      Matsuura, E
    • Journal Title

      Lupus 14・9

      Pages: 736-741

  • [Journal Article] Research around β2-glycoprotein I. a major target for antiphospholipid antibodies.2005

    • Author(s)
      Atsumi, T
    • Journal Title

      Autoimmun 38・5

      Pages: 377-381

  • [Journal Article] Antigenic structures recognized by anti-β2-glycoprotein I auto-antibodies.2005

    • Author(s)
      Kasahara, H
    • Journal Title

      Int Immunol 17・2

      Pages: 1533-1542

  • [Journal Article] Accelerated atherosclerosis in autoimmune rheumatic disease.2005

    • Author(s)
      Shoenfeld, Y
    • Journal Title

      Circulation 112・21

      Pages: 3337-3347

  • [Journal Article] Increase of serum angiopoietin-2 during pregnancy is suppressed in women with preeclampsia.2005

    • Author(s)
      Hirokoshi, K
    • Journal Title

      Am J Hypertens 18:9 pt1

      Pages: 1181-1188

  • [Journal Article] Lymphocyte subpopulations and intima media thickness in primary antiphospholipd syndrome.2005

    • Author(s)
      Ames, PRJ
    • Journal Title

      Lupus 14・10

      Pages: 809-813

  • [Journal Article] Intravenous immunoglobulin and atherosclerosis.2005

    • Author(s)
      Matsuura, E
    • Journal Title

      Clin Rev Allergy Immunol 29・3

      Pages: 311-319

  • [Book] Accelerated atherogenesis and antiphospholipid antibodies. In Hughes Syndrome : Antiphospholipid Syndrome (2nd Edition)(Khamashta M ed.)2006

    • Author(s)
      Matsuura, E
    • Total Pages
      589(501-520)
    • Publisher
      Springer-Verlag, London, UK.
  • [Book] Accelerated atheroma in the antiphospholipid syndrome. In Rheumatic Disease Clinics of North America.(Khamashta MA, ed.)2006

    • Author(s)
      Matsuura, E
    • Publisher
      Elsevier, Amsterdam, The Netherlands(in press)
  • [Book] β2-glycoprotein I autoantibodies. Autoantibodies. 2nd Edition. Elsevier, Amsterdam, The Netherlands.(Shoenfeld Y, Gershwin ME eds.)2006

    • Author(s)
      Matsuura, E
    • Publisher
      Elseveier, Amsterdam, The Netherlands(in press)
  • [Book] 抗リン脂質抗体症候群.図説アートマニュアル.(永井書店、大阪)2006

    • Author(s)
      小林和子
    • Publisher
      永井書店、大阪(印刷中)

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Published: 2007-04-02   Modified: 2016-04-21  

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