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Modified structure and biological activities for oxidized LDL present in vivo searching for a better model for the physiological oxidized LDL

Research Project

Project/Area Number 13672303
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

ITABE Hiroyuki  Teikyo Univ. , Fac. of Pharmaceutical Sciences,Associate Professor, 薬学部, 助教授 (30203079)

Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2001: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywordsoxidized LDL / oxidized phosphatidylcholine / minimally modified LDL / atherosclerosis / HPLC / monoclonal antibody / macrophages / 微小酸化LDL
Research Abstract

It is widely believed that oxidized LDL (OxLDL) is involved in atherogenesis. We have demonstrated the presence of OxLDL in circulating plasma by developing a sensitive method of measuring OxLDL using a monoclonal antibody. Recently, a question arises whether copper-induced oxidation of LDL, which has been widely utilized as a model, reflects the characteristics of OxLDL in vivo. An alternative model for in vivo OxLDL is called minimally modified LDL (MM-LDL) which is prepared under milder conditions. In the present study, various modified LDLs were characterized.
MM-LDL was prepared by the method described by Berliner et al. , in which LDL was dialyzed against PBS containing FeS04 at 4 ℃ for 4 days. While the MM-LDL contained a quarter as much of TBARS compared to copper-induced OxLDL, the amount of conjugated dienes and reactivity to anti-oxidized phosphatidylcholine (OxPC) antibody in the both modified LDLs were almost the same. When aldehyde-containing OxPC in the total lipids extracted from the modified LDLs, 10-fold larger amount of aldehyde-containing OxPC was present in MM-LDL than copper-induced OxLDL. From these results, it is clear that oxidized products and modified structures in the oxidatively modified LDL can be varied depending on the treatment.
The next step for this study is to compare the oxLDL present in vivo with these modified LDL models. In order to do this, a procedure to isolate minute amount of OxLDL from plasma and sensitive methods to determine oxidation products must be improved. As low as 10 pmol of aldehyde-containing OxPC can be detected as fluorescent derivatives, however, even more sensitive analysis was achieved using ESI/MS procedure. Isolation of OxLDL from plasma was not successful so far by ion-exchange HPLC or density gradient ultracentrifugation. We are currently trying an immuno-precipitaion procedure for this purpose.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (35 results)

All Other

All Publications (35 results)

  • [Publications] Higashi, Y., et al.: "Distribution of microsomal triglyceride transfer protein within sub-endoplasmic reticulum regions in human hepatoma cells"Biochim.Biophys.Acta. 1581. 127-136 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nishi, K., et al.: "Oxidized LDL in carotid plaques and plasma associates with plaque instability"Arterioscler.Thromb.Vasc.Biol.. 22. 1649-1654 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Azumi, H., et al.: "Superoxide generation in directional coronary atherectomy specimens of patients with angina pectris. Important role of p22phox-based NADH/NADPH oxidase"Arterioscler.Thromb.Vasc.Biol.. 22. 1838-1844 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ehara, S., et al.: "Pathophysiological role of oxidized low-density lipoprotein in plaque instability in coronary artery diseases"J.Diabetes Compl.. 16. 60-64 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Itabe, H.: "Oxidized low density lipoprotein : What is understood and what remains to be clarified"Biol.Pharm.Bull.. 26. 1-9 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 板部洋之: "モノクローナル抗体を用いた酸化LDLの高感度定量と動脈硬化"薬学雑誌. 122. 745-753 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 板部洋之: "酸化LDL濃度と血管障害"血管医学. 3. 33-40 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 板部洋之: "生体内酸化LDLの動態"別冊・医学のあゆみ「高脂血症と動脈硬化」(馬渕宏編). 163-167 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Higashi, Y., Itabe, H., Fukase, H., Mori, M.,Fujimoto, Y., Sato, R., Imanaka, T. and Takano, T: "Distribution of microsomal triglyceride transfer protein within sub-endoplasmic reticulum regions in human hepatoma cells"Biochim. Biophys. Acta. 1581. 127-136 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ehara, S., Ueda, M., Naruko, T., Haze, K., Ogami,M., Ikura, Y., Itabe, H., Komatsu, R., Yoshiyama, M.,Takeuchi, K. and Yoshikawa, J.: "Pathophysiological role of oxidized low-density lipoprotein in plaque instability in coronary artery diseases"J. Diabetes Compl.. 16. 60-64 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nishi, K., Itabe, H., Uno, M., Kitazato K. T.,Horiguchi, H., Shinno, K. and Nagahiro S.: "Oxidized LDL in carotid plaques and plasma associates with plaque instability"Arterioscler. Thromb. Vasc. Biol.. 22. 1649-1654 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Azumi, H., Inoue, N., Ohashi, Y., Terashima, M.,Mori, T., Fujita, H., Awano, K., Kobayashi, K., Maeda,K., Hata, K., Shinke, T., Kobayashi, S., Hirata, K.,Kawashima, S., Itabe, H., Hayashi, Y., Imajo-Ohmo, S.,Itoh, H. and Yokoyama, M.: "Superoxide generation in directional coronary atherectomy specimens of patients with angina pectris. Important role of p22phox-based NADH/NADPH oxidase"Arterioscler. Thromb. Vasc. Biol.. 22. 1838-1844 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Itabe, H.: "Oxidized low density lipoprotein : What is understood and what remains to be clarified"Biol. Pharm. Bull.. 26. 1-9 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Higashi, Y., et al.: "Distribution of microsomal triglyceride transfer protein within sub-endoplasmic reticulum regions in human hepatoma cells"Biochim. Biophys. Acta. 1581. 127-136 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nishi, K., et al.: "Oxidized LDL in carotid plaques and plasma associates with plaque instability"Arterioscler. Thromb. Vasc. Biol.. 22. 1649-1654 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Azumi, H., et al.: "Superoxide generation in directional coronary atherectomy specimens of patients with angina pectris. Important role of p22phox-based NADH/NADPH oxidase"Arterioscler. Thromb. Vasc. Biol.. 22. 1838-1844 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ehara, S., et al.: "Pathophysiological role of oxidized low-density lipoprotein in plaque instability in coronary arterv diseases"J. Diabetes Compl.. 16. 60-64 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Itabe, H.: "Oxidized low density lipoprotein : What is understood and what remains to be clarified"Biol. Pharm. Bull.. 26. 1-9 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] 板部洋之: "モノクローナル抗体を用いた酸化LDLの高感度定量と動脈硬化"薬学雑誌. 122. 745-753 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 板部洋之: "酸化LDL濃度と血管障害"血管医学. 3. 33-40 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 板部洋之: "生体内酸化LDL動態"別冊・医学のあゆみ「高脂血症と動脈硬化」(馬渕宏編). 163-167 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ishikawa, K., et al.: "Heme oxygenase-1 inhibits atherosclerotic lesion formation in LDL receptor knockout mice"Circ.Res.. 88. 506-512 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ehara, S., et al.: "Oxidized low density lipoprotein relates to plaque destabilization in human coronary atherosclerotic lesions"Circulation. 103. 1955-1960 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Itabe, H., Takano, T.: "Oxidized low density lipoprotein: The occurrence and metabolism in circulation and in foam cells"J.Atheroscler.Thromb.. 7. 123-130 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sugawara, D., et al.: "Heme oxygenase-1 inhibits atherogenesis in Watanabe heritable hyperlipidemic rabbits"Circulation. 104. 1831-1836 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Mori, M., et al.: "Foam cells containing lipid droplets enriched with free cholestrol by hyperlipidemic serum"J.Lipid Res.. 42. 1771-1781 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sakata, N., et al.: "Glycoxidation and lipid peroxidation of low-density lipoprotein can synergistically enhance atherogenesis"Cardiovasc.Res.. 49. 466-475

    • Related Report
      2001 Annual Research Report
  • [Publications] Ohtani, K., et al.: "The membrane type collectin CL-P1 is a scavenger receptor on vascular endothelial cells"J.Biol.Chem.. 276. 44222-44228 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Higashi, Y., et al.: "Distribution of microsomal triglyceride transfer protein within subendoplasmic reticulum regions in human hepatoma cells"Biochim.Biophys.Acta. (印刷中). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] 板部洋之, 高野達哉: "脂質・リポ蛋白質代謝の分子機構 リン脂質"日本臨床(増刊号2「高脂血症(上)」). 59. 29-36 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 板部洋之: "生活習慣病と酸化ストレス"ファルマシア. 37. 805-809 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 板部洋之: "酸化LDL中の酸化リン脂質とその意義"動脈硬化. 28. 63-68 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 板部洋之: "酸化リン脂質と動脈硬化"循環器科. 50. 200-208 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 板部洋之: "酸化リン脂質と動脈硬化"血管医学. 2. 614-622 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 板部洋之 他(計28名): "動脈硬化成因カンファレンス講演記録"ライフサイエンス出版. 354 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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