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Oxidized lipoproteins released from atherosclerotic lesions

Research Project

Project/Area Number 12672121
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionTeikyo University

Principal Investigator

TAKANO Tatsuya  Teikyo Univ., Pharm. Sci., Prof., 薬学部, 教授 (40124995)

Co-Investigator(Kenkyū-buntansha) HIGASHI Yusuke  Teikyo Univ., Pharm. Sci., Res. Ass., 薬学部, 助手 (60286979)
MORI Masahiro  Teikyo Univ., Pharm. Sci., Res. Ass., 薬学部, 助手 (00230079)
ITABE Hiroyuki  Teikyo Univ., Pharm. Sci., Prof. Ass., 薬学部, 助教授 (30203079)
FUJIMOTO Yasuyuki  Teikyo Univ., Pharm. Sci., Res. Ass., 薬学部, 助手 (60317724)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2001: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2000: ¥2,400,000 (Direct Cost: ¥2,400,000)
Keywordsoxidized LDL / Myocardial infarction / Macorphage / Atherectomy / Monoclonal antibody / モノクローナル抗体 / 動脈硬化 / 腎疾患 / 体外診断薬 / 酸化リポタンパク質
Research Abstract

We developed a sandwich ELISA method to measure OXLDL levels using a novel anti-OXLDL monoclonal antibody (FOHla/DLH3) and an anti-apolipoprotein B polyclonal antibody. FOHla/DLH3 is specific for ox-LDL and does not bind to native, acetylated, MDA-treated, or glycated LDL.
With the use of this new and highly sensitive method, we measured the levels of OXLDL in patients with acute myocardial infarction (AMI), unstable angina pectoris (UAP), and stable angina pectoris (SAP). In addition, we immuno-histochemically studied the presence of oxLDL in coronary atherectomy specimens taken from the culprit lesions responsible for SAP and UAP, although oxLDL levels in these patients were not available. Hence, the study is based on a cohort of patients with similar clinical characteristics but in whom different methodologies were applied. The first group contains patients presenting with various degrees of signs and symptoms of a coronary syndrome in whom oxLDL levels were determined and correlated with the severity of the syndrome. The second group of patients also presented with angina pectoris, but in those patients, only atherectomy specimens obtained from culprit lesions were available and studied immuno-histochemically for the presence of oxLDL.
In conclusions, this study demonstrates that OXLDL levels show a significant positive correlation with the severity of acute coronary syndromes and that the more severe lesions also contain a significantly higher percentage of OXLDL positive macrophages. These observations suggest that increased levels of OXLDL relate to plaque instability in human coronary atherosclerotic lesions.

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (42 results)

All Other

All Publications (42 results)

  • [Publications] Mori M., Takano T., et al.: "Formation of lipid droplets enriched with phospholipid-cholesterol complexes in foam cells by hyperlipidemic serum"J.Lipid Res.. 42. 1771-1781 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ehara S., Takano T., et al.: "Oxidized low density lipoprotein relates to plaque destabilization in human coronary atherosclerotic lesions.Circulation"Circulation. April17. 1955-1960 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Noriyuki S., Takano T., et al.: "Glycoxidation and lipid peroxidation of low-density lipoprotein can synergistically enhance atherogenesis"Cardiovascular Res.. 49. 466-475 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Morita M., Takano T., et al.: "Insulin-degrading enzyme exists inside of rat liver peroxisomes and degrades oxidized protein"Cell Structure and Function. 25. 309-315 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Itabe H., Takano T., et al.: "Oxidized low density lipoprotein : The occurrence and metabolism in circulation and in foam cell"J.Atheroscler.Thromb. 7. 123-131 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Khono, H., Takano, T., et al.: "Simple and practical Sandwich-Type Enzyme Immunoassay for Human Oxidatively modified Low Density Lipoprotein Using Antioxidized Phosphatidylcholine Monoclonal Antibody and Human Apolipoprotein-B Antibody"Clinical Biochem.. 33(4). 243-253 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Itabe, H., Takano, T., et al.: "Preparation of radioactive aldehyde-containing phosphatidyicholine"Analyticlal Biochem.. 285. 151-155 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Toshima, S., Takano, T., et al.: "Circulating oxidized low density lipoprotein levels-A biochemical risk marker for coronary heart disease"Arterioscler Thromb Vasc Biol.. 20. 2243-2247 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Itabe, H., Takano, T., et al.: "Lysosomal accumulation of oxidized phosphatidylcholine-apolipoprotein B complex in macrophages : intracellular fate of oxidized low density lipoprotein"Biochim.Biophys.Acta. 1487. 233-245 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Fukasawa, M., Takano, T., et al.: "Reduction of Sphingomyelin Level without Accumulation of Ceramide in Chinese Hamster Ovary Cells Affects Detergent-resistant Membrane Domains and Enhances Cellular Cholesterol Efflux to Methyl-b-cyclodextrin"J.Biol.Chem.. 275(44). 34028-34034 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 板部 洋之, 高野 達哉: "日本臨床"リポ蛋白代謝の分子機構. 29-36 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Mori M., Takano T. et al.: "Formation of lipid droplets enriched with phospholipid-cholesterol complexes in foam cells by hyperlipidemic serum."J. Lipid Res.. 42. 1771-1781 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ehara S., Takano T. et al.: "Oxidized low density lipoprotein relates to plaque destabilization in human coronary atherosclerotic lesions. Circulation"Circulation. April 17. 1955-1960 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] NOriyuki S., Takano T. et al.: "Glycoxidation and lipid peroxidation of low-density lipoprotein can synergistically enhance atherogenesis."Cardiovascular Res.. 49. 466-475 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Morita M., Takano T. et al.: "Insulin-degrading enzyme exists inside of rat liver peroxisomes and degrades oxidized protein"Cell Structure and Function. 25. 305-309 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Itabe H., Takano T. et al.: "Oxidized low density lipoprotein: The occurrence and metabolism in circulation and in foam cell"J. Atheroscler. Thromb. 7. 123-131 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Khono H., Takano T. et al.: "Simple and practical sandwich-type enzyme immunoassay for human oxidatively modified low density lipoprotein using antioxidized phosphatidylcholine monoclonal..."Clinical Biochem. 33(4). 243-253 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Itabe H., Takano T. et al.: "Preparation of radioactive aldehyde-containing phosphatidylcholine"Analytical Biochem. 285. 151-155 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Toshima S., Takano T. et al.: "Circujating oxidized low density lipoprotein levels - A biochemical risk marker for coronary heart disease"Arterioscler Thromb Vasc Biol. 20. 2243-2247 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Itabe H., Takano T. et al.: "Lysosomal accumulation of oxidized phosphatidylcholine-apolipoprotein B complex in macrophages : intracellular fate of oxidized low density lipoprotein"Biochim. Biophys. Acta.. 1487. 233-245 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Fukawa M., Takano T. et al.: "Reduction of sphingomyelin level without accumulation of ceramide in Chinese hamster ovary cells affects detergent-resistant membrane domains and..."J. Biol. Chem.. 275(44). 34028-34034 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Mori M., Takano T.et al: "Formation of lipid droplets enriched with phospholipid-cholesterol complexes in foam cells by hyperlipidemic serum"J.Lipid Res.. 42. 1771-1781 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ehara S., Takano T et al: "Oxidized low density lipoprotein relates to plaque destabilization in human coronary atherosclerotic lesions.Circulation"Circulation. April 17. 1955-1960 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Noriyuki S., Takano T.et al: "Glycoxidation and lipid peroxidation of low-density lipoprotein can synergistically enhance atherogenesis"Cardiovascular Res.. 49. 466-475 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Morita M., Takano T.et al: "Insulin-degrading enzyme exists inside of rat liver peroxisomes and degrades oxidized protein"Cell Structure and Function. 25. 309-315 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Itabe H., Takano T.et al: "Oxidized low density lipoprotein : The occurrence and metabolism in circulation and in foam cell"J.Atheroscler.Thromb.. 7. 123-131 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Khono, H., Takano, T.et.al.: "Simple and practical sandwich-type enzyme immunoassay for human oxidatively modified low density lipoprotein using antioxidized phosphatidylcholine monoclonal..."Clinical Biochem.. 33(4). 243-253 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Itabe, H., Takano, T.et.al.: "Preparation of radioactive aldehyde-containing phosphatidylcholine"Analyticlal Biochem.. 285. 151-155 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Toshima, S., Takano, T.et.al.: "Circulating oxidized low density lipoprotein levels-A biochemical risk marker for coronary heart disease"Arterioscler Thromb Vasc Biol.. 20. 2243-2247 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Itabe, H., Takano, T.et.al.: "Lysosomal accumulation of oxidized phosphatidylcholine-apolipoprotein B complex in macrophages : intracellular fate of oxidized low density lipoprotein"Biochim.Biophys.Acta. 1487. 233-245 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Fukasawa, M., Takano, T.et.al.: "Reduction of sphingomyelin level without accumulation of ceramide in chinese hamster ovary cells affects detergent-resistant membrane domains and..."J.Biol.Chem.. 275(44). 34028-34034 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] 板部 洋之, 高野 達哉: "日本臨床"リポ蛋白代謝の分子機構. 29-36 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Khono,H.,Takano,T. et,al.: "Simple and practical sandwich-type enzyme immunoassay for human oxidatively modified low density lipoprotein using antioxidized phosphatidylcholine monoclonal.."Clinical Biochem.. 33(4). 243-253 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Itabe,H.,Takano,T. et.al.: "Preparation of radioactive aldehyde-containing phosphatidylcholine"Analyticlal Biochem.. 285. 151-155 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Toshima,S.,Takano.T. et.al.: "Circulating oxidized low density lipoprotein levels - A biochemical risk marker for coronary heart disease"Arterioscler Thromb Vasc Biol.. 20. 2243-2247 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Itabe,H.,Takano,T. et.al.: "Lysosomal accumulation of oxidized phosphatidylcholine-apolipoprotein B complex in macrophages : intracellular fate of oxidized low density lipoprotein"Biochim.Biophys.Acta. 1487. 233-245 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Fukasawa,M.,Takano,T. et.al.: "Reduction of sphingomyelin level without accumulation of ceramide in chinese hamster ovary cells affects detergent-resistant membrane domains and ...."J.Biol.Chem.. 275(44). 34028-34034 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Imanaka,T.,Takano,T., et.al.: "Characterizaion of the 70-kDa peroxisomal membrane protein, and ATP binding cassette transporter."J.Biol.Chem.. 274(17). 11968-11976 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Mori,M.,Takano,T. et.al.: "Presensce of phospholipid-neutral lipid complex structures in atherosclerotic lesions as detected by a novel monoclonal antibody"J.Biol.Chem.. 274(35). 24824-24837 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Itabe,H.,Takano,T. et.al.: "Metabolism of oxidized phosphatidylcholines formed in oxidized low density lipoprotein by lecithin-cholesterol acyltransferase"J.Biochem.. 126(1). 153-161 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Sakata,N.,Takano,T. et.al.: "Immunohistochemical localization of different epitopes of advanced glycation end products inhuman atherosclerotic lesions."Atherosclerosis. 141. 61-75 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] 板部洋之,高野達哉: "The Lipid"リポ蛋白「酸化」の生化学とリポ蛋白代謝. 236-241 (1999)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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