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Novel methods for measuring urine F2-isoprostanes using LC-MS/MS and the origin of electronegative LDLNovel methods for measuring urine F2-isoprostanes using LC-MS/MS and the origin of electronegative LDL

Research Project

Project/Area Number 18591009
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Metabolomics
Research InstitutionFukuoka University

Principal Investigator

SEGAWA Namiko  Fukuoka University, 医学部, 助教 (80352251)

Co-Investigator(Kenkyū-buntansha) SAKU Keijiro  福岡大学, 医学部, 教授 (40183371)
YOSHINAGA Kazuhiko  福岡大学, 医学部, 講師 (80122761)
MATSUMOTO Naomichi  福岡大学, 医学部, 助教 (20412603)
Project Period (FY) 2006 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥3,880,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥480,000)
Fiscal Year 2008: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2007: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywords動脈硬化学 / 血漿リポ蛋白 / 陰性荷電変性LDL / キャピラリー等速電気泳動法 / 小型化LDL分画 / 超遠心によるリポ蛋白分画 / 中性脂肪リッチリポ蛋白 / very-fast-migrating LDL (vfLDL) / 脂質異常症 / 尿中F_2イソプロスタン / プロスタグランジン / 固相抽出(SPE) / 液クロマトグラフィー(LC) / タンデム質量分析(MS / MS) / 8-iso-prostaglandin F_?2α? / 立体異性体 / 位置異性体 / 尿中F_2-イソプロスタン / 8-iso-prostaglandin F_<2α>
Research Abstract

酸化ストレスのマーカーとして確立されている尿中F2-イソプロスタンはプロスタグランジンの立体異性体であり、多数の立体異性体と位置異性体が存在する。F2-イソプロスタンを高感度・高特異的に測定するために、新規多次元同相抽出法と新規バッファーフリーLC-MS/MS法を開発した。酸化LDLに代表される陰性荷電変性LDLは、マクロファージが好んで合食することが知られている。高コレステロール血症患者において、キャピラリー等速電気泳動(cITP)法により分析した陰性荷電LDL亜分画は、炎症マーカー、動脈硬化性リポ蛋白と関係することを示した。高コレステロール血症患者の血漿中に、中性脂肪リッチリポ蛋白(TRL)と同じ電気泳動泳動度(pre-beta)を有する新たな陰性荷電変性LDL亜分画(very-fast migrating LDL, vfLDL)の存在を発見した。また、vfLDL亜分画は、fast-migrating LDL(fLDL)亜分画と強く相関したが、正常荷電LDL亜分画と相関しなかった。vfLDL亜分画は、fLDLと同様にスタチン薬Rosuvastatinによって低下した。

Report

(4 results)
  • 2008 Annual Research Report   Final Research Report ( PDF )
  • 2007 Annual Research Report
  • 2006 Annual Research Report
  • Research Products

    (21 results)

All 2009 2008 2007 2006

All Journal Article (14 results) (of which Peer Reviewed: 8 results) Presentation (5 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 2 results)

  • [Journal Article] Effects of ROSuvastatin on electronegative LDL as characterized by CapillARY isotachophoresis: The ROSARY study2009

    • Author(s)
      Zhang B., Matsunaga A., Rainwater D.L., Y., Shirai K., Saku K.
    • Journal Title

      Journal of Lipid Research (in press)

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Effects of ROSuvastatin on electronegative LDL as characterized by CapillARY isotachophoresis : The ROSARY study.2009

    • Author(s)
      Zhang B., et al.
    • Journal Title

      Journal of Lipid Research (In press)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Reduction of charge-modified LDL by statin therapy in patients with CHD or CHD risk factors and elevated LDL-C levels: The SPECIAL Study2008

    • Author(s)
      Zhang B. Miura S., Yanagi D, Noda K., Nishikawa H., Matsunaga A., Shirai K., IwataA., Yoshinaどa K. Adachi H.. Imaizumi T., Saku K.
    • Journal Title

      Atherosclerosis 201

      Pages: 353-9

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Control of matrix effects in the analysis of urinary F2-isoprostanes using novel multidimensional solid-phase extraction and LC-MS/MS2008

    • Author(s)
      Zhang B. and Saku K.
    • Journal Title

      Journal of Lipid Research 48

      Pages: 733-44

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Reduction of charge-modified LDL by statin therapy in patients with CHD or CHD risk factors and elevated LDL-C levels : The SPECIAL study2008

    • Author(s)
      Zhang B., et al.
    • Journal Title

      Atherosclerosis 201

      Pages: 353-9

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Reduction of charge-modified LDL by statin therapy in patients with CHD or CHD risk factors and elevated LDL-C levels: The SPECIAL Study2008

    • Author(s)
      Zhang B, et. al.
    • Journal Title

      Atherosclerosis (In press)

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of apoA-I/phosphatidylcholine discs on charge-based LDL subfractions as characterized by capillary isotachophoresis2007

    • Author(s)
      Zhang B, et. al.
    • Journal Title

      Journal of Lipid Research 48

      Pages: 1175-1189

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Control of matrix effects in the analysis of rnary F2-isoprostanes using novel multidilnensional solid-phase extraction and LC-MS/MS2007

    • Author(s)
      Zhang B, et. al.
    • Journal Title

      Journal of Lipid Research 48

      Pages: 733-744

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of apoA-I/phosphatidylcholine discs on charge-based LDL subfractions as characterized by capillary isotachophoresis2007

    • Author(s)
      Zhang B.et al.
    • Journal Title

      Journal of Lipid Research (in press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Control of matrix effects in the analysis of urinary F2-isoprostanes using novel multidimensional solid-phase extraction and LC-MS/MS2007

    • Author(s)
      Zhang B, Saku K
    • Journal Title

      Journal of Lipid Research 48

      Pages: 733-44

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Modulating effects of cholesterol feeding and simvastatin treatment on platelet-activating factor acetylhydrolase activity and lysophosphatidylcholine concentration2006

    • Author(s)
      Zhang B.et al.
    • Journal Title

      Atherosclerosis 186

      Pages: 291-301

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Relation between charge-based apolipoprotein B-containing lipoprotein subfractions and remnant-like particle cholesterol levels2006

    • Author(s)
      Zhang B.et al.
    • Journal Title

      Atherosclerosis 191

      Pages: 153-31

    • Related Report
      2006 Annual Research Report
  • [Journal Article] ApoA-I/phosphatidylcholine discs remodels fast-migrating HDL into slow-migrating HDL as characterized by copillary isotachophoresis2006

    • Author(s)
      Zhang B.et al.
    • Journal Title

      Atherosclerosis 199

      Pages: 95-101

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Association between fast-migrating low-density lipoprotein subfraction as characterized by capillary isotachophoresis and intima-media thickness of carotid artery2006

    • Author(s)
      Zhang B.et al.
    • Journal Title

      Atherosclerosis 187

      Pages: 205-12

    • Related Report
      2006 Annual Research Report
  • [Presentation] HDL-Raising Efficacy and the Effects of ROSuvastatin on Small, Dense Electronegative LDL as Characterized by CapillARY Isotachophoresis: The ROSARY Study2009

    • Author(s)
      Zhang B., Matsunaga A., Miura S, Noda K., Nishikawa H., Uehara, Y., Shirai K., Saku K.
    • Organizer
      第73回日本循環器学会総会・学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2009-03-22
    • Related Report
      2008 Final Research Report
  • [Presentation] HDL-Raising Efficacy and the Effects of ROSuvastatin on Small, Dense Electronegative LDL as Characterized by CapillARY Isotachophoresis : The ROSARY study2009

    • Author(s)
      Zhang B., et al.
    • Organizer
      第73回日本循環器学会総会・学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2009-03-22
    • Related Report
      2008 Annual Research Report
  • [Presentation] Fast-migrating low-density lipoprotein as analyzed by capillary isotachophoresis is related to inflammatory markers and reduced by pravastatin and simvastatin: the SPECIAL study2008

    • Author(s)
      Zhang B. Miura S., Noda K., Nishikawa H., Matsunaga A., Shirai K., IwataA., Yoshinaga K. Saku K.
    • Organizer
      57th Annual Scientific Meeting of American College of Cardiology (ACC2008)
    • Place of Presentation
      シカゴ、米国
    • Year and Date
      2008-03-31
    • Related Report
      2008 Final Research Report
  • [Presentation] Fast-migrating low-density lipoprotein as analyzed by capillary isotachophoresis is related to inflammatory markers and reduced by pravastatin and simvastatin:the SPECIAL study2008

    • Author(s)
      Zhang B, et. al.
    • Organizer
      57th Annual Scientific Meeting of American College of Cardiology(ACC 2008)
    • Place of Presentation
      シカゴ、米国
    • Year and Date
      2008-03-31
    • Related Report
      2007 Annual Research Report
  • [Presentation] Novel Technology for Comprehensive Analyses of Oxidative Stress Biomarkers2007

    • Author(s)
      Zhang B. and Saku K.
    • Organizer
      The 5th Annual Congress of International Drug Discovery Science and Technology (IDDST)
    • Place of Presentation
      Shanghai, P.R. China
    • Year and Date
      2007-05-16
    • Related Report
      2008 Final Research Report
  • [Patent(Industrial Property Rights)] F2-イソプロスタン異性体測定方法2007

    • Inventor(s)
      張波(瀬川波子)、朔啓二郎
    • Industrial Property Rights Holder
      張波(瀬川波子)、朔啓二郎
    • Filing Date
      2007-08-11
    • Related Report
      2008 Final Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] F2-イソプロスタン異性体測定方法2007

    • Inventor(s)
      張 波(瀬川 波子)、朔 啓二郎
    • Industrial Property Rights Holder
      張 波(瀬川 波子)、朔 啓二郎
    • Filing Date
      2007-08-11
    • Related Report
      2007 Annual Research Report
    • Overseas

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Published: 2006-04-01   Modified: 2016-04-21  

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