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"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 Category

Grant-in-Aid for Exploratory Research

Allocation TypeSingle-year Grants
Research Field Laboratory medicine
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)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2005: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
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 / β_2-グリコプロテインI(β_2GPI)
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。

Report

(2 results)
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • Research Products

    (43 results)

All 2006 2005 2004

All Journal Article (33 results) Book (10 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

    • Related Report
      2005 Annual Research Report
  • [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)

    • Related Report
      2005 Annual Research Report
  • [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)

    • Related Report
      2005 Annual Research Report
  • [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)

    • Related Report
      2005 Annual Research Report
  • [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

    • Related Report
      2005 Annual Research Report
  • [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

    • Related Report
      2005 Annual Research Report
  • [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

    • Related Report
      2005 Annual Research Report
  • [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

    • Related Report
      2005 Annual Research Report
  • [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

    • Related Report
      2005 Annual Research Report
  • [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

    • Related Report
      2005 Annual Research Report
  • [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

    • Related Report
      2005 Annual Research Report
  • [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

    • Related Report
      2005 Annual Research Report
  • [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

    • Related Report
      2005 Annual Research Report
  • [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

    • Related Report
      2005 Annual Research Report
  • [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

    • Related Report
      2005 Annual Research Report
  • [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

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Accelerated atherosclerosis in autoimmune rheumatic disease.2005

    • Author(s)
      Shoenfeld, Y
    • Journal Title

      Circulation 112・21

      Pages: 3337-3347

    • Related Report
      2005 Annual Research Report
  • [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

    • Related Report
      2005 Annual Research Report
  • [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

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Intravenous immunoglobulin and atherosclerosis.2005

    • Author(s)
      Matsuura, E
    • Journal Title

      Clin Rev Allergy Immunol 29・3

      Pages: 311-319

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Characterization of a murine anti-laminin-1 monoclonal antibody (AK8) produced by immunization with mouse-derived laminin-12005

    • Author(s)
      Kondo, A
    • Journal Title

      Clinical and Developmental Immunology 12・1

      Pages: 67-73

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Significance of valine/leucine^<247> polymorphism of β_2-glycoprotein I in antiphospholipid syndrome : increased reactivity of anti-β_2-glycoprotein I autoantibodies to the valine^<247> β_2-glycoprotein I variant2005

    • Author(s)
      Yasuda, S
    • Journal Title

      Arthritis and Rheumatism 52・1

      Pages: 212-218

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Binding of β_2-glycoprotein I to anionic phospholipids facilitates processing and presentation of a cryptic epitope that activates pathogenic autoreactive T cells2005

    • Author(s)
      Kuwana, M
    • Journal Title

      Blood (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Pregnancy loss and endometriosis : pathogenic role of anti-laminin-1 autoantibodies2005

    • Author(s)
      Inagaki, J
    • Journal Title

      Annals of New York Academy of Science (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] The role of innate and adaptive immunity to oxidized low-density lipoprotein in the development of atherosclerosis2005

    • Author(s)
      Kobayashi, K
    • Journal Title

      Annals of New York Academy of Science (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Oxidized low-density lipoprotein/β_2-glycoprotein I complexes and autoantibodies in patients with type 2 diabetes mellitus2005

    • Author(s)
      Lopez, LR
    • Journal Title

      Annals of New York Academy of Science (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Anti-laminin-1 autoantibodies and reproductive failure2005

    • Author(s)
      Kondo, A
    • Journal Title

      American Journal of Reproductive Immunology (in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Oxidized low-density lipoprotein/β_2-glycoprotein I complexes and autoantibodies to oxLig-1/β_2-glycoprotein I in patients with systemic lupus erythematosus and antiphospholipid syndrome2004

    • Author(s)
      Lopez, D
    • Journal Title

      American Journal of Clinical Pathology 121・3

      Pages: 426-436

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Nicked β_2-glycoprotein I : A marker of cerebral infarct and a novel role in the negative feedback pathway of extrinsic fibrinolysis2004

    • Author(s)
      Yasuda, S
    • Journal Title

      Blood 103・10

      Pages: 3766-3772

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Clinical significance of serum oxidized low-density lipoprotein/β_2-glycoprotein I complexes-in patients with chronic renal diseases2004

    • Author(s)
      Kasahara, J
    • Journal Title

      Nephron Clinical Practice 98・1

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Are anti-oxidized low-density lipoprotein antibodies pathogenic or protective?2004

    • Author(s)
      Shoenfeld, Y
    • Journal Title

      Circulation 110・17

      Pages: 2552-2558

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Are oxidized LDL/β_2-glycoprotein I complexes pathogenic antigens in autoimmune-mediated atherosclerosis?2004

    • Author(s)
      Matsuura, E
    • Journal Title

      Clinical and Developmental Immunology 11・2

      Pages: 103-111

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Anti-laminin-1 autoantibodies, pregnancy loss and endometriosis2004

    • Author(s)
      Inagaki, J
    • Journal Title

      Clinical and Developmental Immunology 11・3-4

      Pages: 261-266

    • Related Report
      2004 Annual Research Report
  • [Book] Accelerated atherogenesis and antiphospholipid antibodies. In Hughes Syndrome : Antiphospholipid Syndrome (2nd Edition)(Khamashta M ed.)2006

    • Author(s)
      Matsuura, E
    • Total Pages
      589
    • Publisher
      Springer-Verlag, London, UK.
    • Related Report
      2005 Annual Research Report
  • [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)
    • Related Report
      2005 Annual Research Report
  • [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)
    • Related Report
      2005 Annual Research Report
  • [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)
    • Related Report
      2005 Annual Research Report
  • [Book] Hughes syndrome : antiphospholipid syndrome (2nd edition), Atherogenesis and antiphospholipid antibodies2005

    • Author(s)
      Matsuura, E
    • Publisher
      Springer (London, UK)(in press)
    • Related Report
      2004 Annual Research Report
  • [Book] Systemic lupus erythematosus (fourth edition), Immunology of antiphospholipid antibodies and cofactors2004

    • Author(s)
      Atsumi, T
    • Publisher
      Elsevier Science BV (Amsterdam, The Netherlands)
    • Related Report
      2004 Annual Research Report
  • [Book] Focus on atherosclerosis research, Oxidized low-density lipoprotein complexed with β_2-glycoprotein I as a common metabolic form in atherogenesis and autoimmune-mediated atherosclerosis. Roles of antibodies on atherosclerosis2004

    • Author(s)
      Matsuura, E
    • Publisher
      Nova Science Publishers (New York, USA)
    • Related Report
      2004 Annual Research Report
  • [Book] Recent research of developments in lipids (Vol 7), Autoimmune-mediated atherosclerosis : pathogenic role of oxLDL/β_2GPI complexes2004

    • Author(s)
      Lopez, LR
    • Publisher
      Transworld Research Network (Kerala, India)
    • Related Report
      2004 Annual Research Report
  • [Book] Autoantigens, autoantibodies, antoimmunity (Vol 4), Anti-laminin-1 autoantibodies in reproductive failure : animal and human studies2004

    • Author(s)
      Inagaki, J
    • Publisher
      Pabst Science Publisher (Lengerich, Germany)
    • Related Report
      2004 Annual Research Report
  • [Book] Autoantigens, autoantibodies, antoimmunity (Vol 4), Atheorogenic role of protein-modified oxidized low-density lipoproteins and their autantibodies2004

    • Author(s)
      Matsuura, E
    • Publisher
      Pabst Science Publisher (Lengerich, Germany)
    • Related Report
      2004 Annual Research Report

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

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