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Pathophysiology of high remnant lipoproteinemia underlying atherosclerotic disease in Japan and development of a new assay for remnant lipoproteins

Research Project

Project/Area Number 16590455
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Laboratory medicine
Research InstitutionOsaka University

Principal Investigator

YAMAMURA Taku  Osaka University, Graduate School of Medicine, Division of Health Sciences, Professor, 医学系研究科, 教授 (20132938)

Co-Investigator(Kenkyū-buntansha) ISHIGAMI Masato  Osaka University, Graduate School of Medicine, Division of Health Sciences, Assistant Professor, 医学系研究科, 助手 (10379266)
Project Period (FY) 2004 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2005: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsHyperlipidemia / Lipoprotein / Remnant lipoprotein / Atherosclerosis / Cholesterol / Postprandial hyperlipidemia / Statin / RLP-C / トリグリセリド / 血清脂質 / TG-richリポ蛋白
Research Abstract

Recent studies have demonstrated that impaired clearance of chylomicron remnant causes postprandial hyper-lipidemia (PPHL), which suggested as one of the risk factors for coronary heart disease (CHD). Furthermore, the increase in very low density lipoprotein (VLDL) remnant in metabolic syndrome (visceral fat syndrome) is an important therapeutic target for the prevention of CHD in developed countries. The measurement of serum remnant concentrations, however, remains complicated and there are as yet no systems which can work on automated analyzers. In this study, we developed a new assay for serum remnant cholesterol using specific detergents and investigated its significance for PPHL.
Remnant lipoproteins in serum were selectively homogenized by specific detergents and phospholipase D followed by enzymatic determination of cholesterol content as remnant lipoprotein-cholesterol (RemL-C). Healthy controls (n=39), type IIa (Ha HL, n=3), and type IIb HL, n=6) hyperlipoproteinemic patients w … More ere investigated. Type IIa and IIb HL were subjected to an oral fat loading test (30 g fat/m^2) before and after atorvastatin treatment (10 mg/day) for 4 weeks. Furthermore, we used gel filtration to analyze hypertriglyceridemic serum. The apolipoprotein (apo) B-48 concentrations were assessed with the chemiluminescence method using a monoclonal antibody to apoB-48 established by us.
In healthy controls, the mean fasting value (MEAN) and standard deviation (SD) of RemL-C were 3.4 and 1.4 mg/dL, respectively. RemL-C of lib HL was higher than the normal range (MEAN + 2SD). Oral fat loading test results showed that in both IIa and lib HL, the RemL-C peaked 1 or 2 hrs behind the TG peak. Atorvastatin treatment reduced the area under the curve of TG and RemL-C drastically especially in IIb HL. In the gel filtra-tion analysis, the peak of RemL-C was observed at the position of so-called large VLDL and coincided with the peak of apoB-48. These findings demonstrate that our assay provides a simple protocol for general use for remnant cholesterol measurement. Atorvastatin was found to improves PPHL, at least partly through a mechanism associated with exogenous lipoprotein metabolism. Less

Report

(4 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • Research Products

    (16 results)

All 2007 2006 2005 2004

All Journal Article (11 results) Book (5 results)

  • [Journal Article] Genetic variants in PCSK9 in the Japanese population : Rare genetic variants in PCSK9 might collectively contribute to plasma LDL cholesterol levels in the general population2007

    • Author(s)
      Yasuko Miyake
    • Journal Title

      Atherosclerosis (印刷中)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Genetic variants in PCSK9 in the Japanese population : Rare genetic variants in PCSK9 might collectively contribute to plasma LDL cholesterol levels in the general population.2007

    • Author(s)
      Miyake, Y., Kimura, R., Kokubo, Y., Okayama, A., Tomoike, H., Yamamura, T., Miyata, T.
    • Journal Title

      Atherosclerosis (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] レムナントリポ蛋白の代謝と臨床的意義2006

    • Author(s)
      山村 卓
    • Journal Title

      Progress Medicine 26・10

      Pages: 2483-2498

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] 脂質代謝異常を探る新たなツールとしての臨床検査 低脂血症の病因、診断2006

    • Author(s)
      石神雅人, 山下静也, 山村 卓
    • Journal Title

      臨床化学 85・3

      Pages: 199-205

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] 生活習慣病の最前線アポ蛋白異常と脂質代謝異常2005

    • Author(s)
      山村 卓
    • Journal Title

      Molecular Medicine Vol.42 (臨時増刊号)

      Pages: 77-85

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] 高脂血症・肥満と精査2005

    • Author(s)
      石神雅人
    • Journal Title

      臨床と研究 82・8

      Pages: 77-85

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary 2005 Annual Research Report
  • [Journal Article] 生活習慣病の最前線 アポ蛋白異常と脂質代謝異常2005

    • Author(s)
      山村 卓
    • Journal Title

      Molecular Medicine Vol.42 臨時増刊号

      Pages: 77-85

    • Related Report
      2005 Annual Research Report
  • [Journal Article] アポE異常症2004

    • Author(s)
      山村 卓
    • Journal Title

      医学のあゆみ(別冊 : 糖尿病・代謝症候群) (別冊)

      Pages: 300-302

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] アポリポ蛋白B2004

    • Author(s)
      山村 卓
    • Journal Title

      日本臨床 62 (Suppl.12)

      Pages: 105-109

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] アポE異常症2004

    • Author(s)
      山村 卓
    • Journal Title

      医学のあゆみ(別冊:糖尿病・代謝症候群) 別冊

      Pages: 300-302

    • Related Report
      2004 Annual Research Report
  • [Journal Article] アポリポ蛋白B2004

    • Author(s)
      山村 卓
    • Journal Title

      日本臨床 62(Suppl.12)

      Pages: 105-109

    • Related Report
      2004 Annual Research Report
  • [Book] III型高脂血症の診断はどうすればいいのですか?「トリグリセライドと動脈硬化-メタボリックシンドロームの観点から」(寺本民生、編)2006

    • Author(s)
      山村 卓, 石神偉人
    • Total Pages
      147
    • Publisher
      医薬ジャーナル社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Book] III 型高脂血症の診断はどうすればいいのですか?「トリグリセライドと動脈硬化-メタボリックシンドロームの観点から」(寺本民生、編)2006

    • Author(s)
      山村 卓, 石神眞人
    • Total Pages
      147
    • Publisher
      医薬ジャーナル社
    • Related Report
      2006 Annual Research Report
  • [Book] 糖尿病と遺伝子(分担執筆)2005

    • Author(s)
      石神眞人
    • Total Pages
      266
    • Publisher
      文光堂
    • Related Report
      2005 Annual Research Report
  • [Book] エクセルナース[検査編]2004

    • Author(s)
      山村 卓
    • Total Pages
      595
    • Publisher
      メディカルレビュー社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Book] エクセルナース[検査編](分担執筆)2004

    • Author(s)
      山村 卓
    • Total Pages
      595
    • Publisher
      メディカルレビュー社
    • Related Report
      2004 Annual Research Report

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

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