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Role of serum mass and activity of endothelial lipase in serum high-density lipoprotein cholesterol level in humans

Research Project

Project/Area Number 21590897
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionKobe University

Principal Investigator

ISHIDA Tatsuro  神戸大学, 医学部附属病院, 准教授 (00379413)

Co-Investigator(Kenkyū-buntansha) HIRATA Ken-ichi  神戸大学, 大学院・医学研究科, 教授 (20283880)
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords脂質代謝 / 循環器 / 血管内皮 / リポ蛋白代謝 / リパーゼ / 脂質異常症 / 動脈硬化 / 臨床 / 生活習慣病 / 高比重リポ蛋白 / 臨床検査
Research Abstract

High-density lipoprotein cholesterol(HDL-C) has a variety of athero-protective actions. Endothelial lipase(EL) hydrolyzes phospholipids in the HDL particle and promotes its catabolism. However, the role of EL in HDL-C levels and atherosclerosis in humans has not been fully elucidated. In this study, we further investigated the role of plasma concentration and activity of EL in HDL-C levels in human subjects.
We have established a novel ELISA system for plasma EL mass by using two monoclonal antibodies against human EL. EL-specific plasma phospholipase activity was measured using a fluorogenic phospholipid as a substrate, after plasma EL protein was immunopricipited using anti-EL antibodies. The plasma EL mass and activity were inversely correlated with plasma HDL-C levels. In addition, the EL mass or activity in patients with cardiovascular diseases was significantly higher than those in patients with cardiovascular diseases. The EL mass or activity was correlated with coronary risk factors including cigarette smoking, high-sensitive CRP, and dyslipidemia.
In conclusion, plasma EL mass and activity are determinants of plasma HDL-C levels, and correlated with risks in cardiovascular diseases. Because inhibition of plasma EL activity increased anti-inflammatory HDL particles, EL may represent a novel target for HDL-raising pharmaceutical interventions for patients with low HDL levels.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (47 results)

All 2012 2011 2010 2009

All Journal Article (25 results) (of which Peer Reviewed: 9 results) Presentation (19 results) Book (3 results)

  • [Journal Article] The Effect of Poloxamer 407 on the Functional Properties of HDL In Mice2012

    • Author(s)
      Yasuda T, Johnston TP, Shinohara M, Inoue M, Ishida T
    • Journal Title

      Pharm Pharmacol

      Volume: 64(5) Pages: 677-87

    • Related Report
      2011 Final Research Report
  • [Journal Article] Endothelial lipase mediates hdl levels in normal and hyperlipidemic rabbits2012

    • Author(s)
      Zhang J, Yu Y, Nakamura K, Koike T, Waqar AB, Zhang X, Liu E, Nishijima K, Kitajima S, Shiomi M, Qi Z, Yu J, Graham MJ, Crooke RM, Ishida T, Hirata K, Hurt-Camejo E, Chen YE, Fan J
    • Journal Title

      J Atheroscler Thromb

      Volume: 19(3) Pages: 213-26

    • NAID

      130004444589

    • Related Report
      2011 Final Research Report
  • [Journal Article] FGD5 Mediates Pro-angiogenic Activity of Vascular Endothelial Growth Factor in Human Vascular Endothelial Cells2012

    • Author(s)
      Kurogane Y, Miyata M, Kubo Y, Nagamatsu Y, Ishida T, Kundu RK, Quertermous T, Hirata K, Rikitake Y
    • Volume
      32(4)
    • Pages
      988-96
    • Related Report
      2011 Final Research Report
  • [Journal Article] The Effect of Poloxamer 407 on the Functional Properties of HDL In Mice2012

    • Author(s)
      Yasuda T., et al
    • Journal Title

      J Pharm Pharmacol

      Volume: (In press)(掲載確定)(未定)

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Endothelial Lipase Mediates HDL Levels in Normal and Hyperlipidemic Rabbits2012

    • Author(s)
      Zhang J, et al
    • Journal Title

      J Atheroscler Thromb

      Volume: (In press)(掲載確定)

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] FGD5 Mediates Pro-angiogenic Activity of Vascular Endothelial Growth Factor in Human Vascular Endothelial Cells2012

    • Author(s)
      Kurogane Y, et al
    • Journal Title

      Arterioscler Thromb Vasc Biol

      Volume: 32 Pages: 988-996

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Orally Administered Eicosapentaenoic Acid Induces Rapid Regression of Atherosclerosis Via Modulating the Phenotype of Dendritic Cells in LDL Receptor-Deficient Mice2011

    • Author(s)
      Nakajima K, Yamashita T, Kita T, Takeda M, Sasaki N, Kasahara K, Shinohara M, Rikitake Y, Ishida T, Yokoyama M, Hirata K
    • Journal Title

      Arterioscler Thromb Vasc Biol

      Volume: 31(9) Pages: 1963-72

    • Related Report
      2011 Final Research Report
  • [Journal Article] Pitavastatin reduces elevated IL-18 levels in Japanese subjects with hypercholesterolemia : Sub-analysis of Kansai Investigation of Statin for Hyperlipidemic Intervention in Metabolism and Endocrinology(KISHIMEN)2011

    • Author(s)
      Fujioka Y, Fukuda A, Ishida T, Kagimoto S, Nakamura Y, Iwakura A, Hara K, Yamamoto T, Kuroe A, Ohya M, Fujimoto S, Hamamoto Y, Honjo S, Ikeda H, Nabe K, Tsuda K, Taniguchi A, Tanaka K, Koshiyama H, Kume N, Hirata K
    • Journal Title

      J Atheroscler Thromb

      Volume: 18(1) Pages: 8-15

    • NAID

      130004444473

    • Related Report
      2011 Final Research Report
  • [Journal Article] Targeted deletion of endothelial lipase increases HDL particles with anti-inflammatory properties both in vitro and in vivo2011

    • Author(s)
      Hara T, Ishida T, Kojima Y, Tanaka H, Yasuda T, Shinohara M, Toh R, Hirata K
    • Journal Title

      J. Lipid Res

      Volume: 52(1) Pages: 57-67

    • Related Report
      2011 Final Research Report
  • [Journal Article] Orally Administered Eicosapentaenoic Acid Induces Rapid Regression of Atherosclerosis Via Modulating the Phenotype of Dendritic Cells in LDL Receptor-Deficient Mice2011

    • Author(s)
      Nakajima K, et al
    • Journal Title

      Arterioscler Thromb Vase Biol

      Volume: 31 Pages: 1963-72

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Targeted deletion of endothelial lipase increases HDL particles with anti-inflammatory properties both in vitro and in vivo.2011

    • Author(s)
      Hara T, Ishida T, et al.
    • Journal Title

      J Lipid Res.

      Volume: 52 Pages: 57-67

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Oral administration of an active form of vitamin D3(calcitriol) decreases atherosclerosis in mice by inducing regulatory T cells and immature dendritic cells with tolerogenic functions2010

    • Author(s)
      Takeda M, Yamashita T, Sasaki N, Nakajima K, Kita T, Shinohara M, Ishida T, Hirata K
    • Journal Title

      Arterioscler Thromb Vasc Biol

      Volume: 30(12) Pages: 2495-503

    • Related Report
      2011 Final Research Report
  • [Journal Article] Update on the role of endothelial lipase in HDL metabolism, reverse cholesterol transport, and atherosclerosis2010

    • Author(s)
      Yasuda T, Ishida T, Rader DJ
    • Journal Title

      Circ J

      Volume: 74(11) Pages: 2263-70

    • Related Report
      2011 Final Research Report
  • [Journal Article] Endothelial cell-selective adhesion molecule modulates atherosclerosis through plaque angiogenesis and monocyteendothelial interaction2010

    • Author(s)
      Inoue M, Ishida T, Yasuda T, Toh R, Hara T, Cangara HM, Rikitake Y, Taira K, Sun L, Kundu RK, Quertermous T, Hirata K
    • Journal Title

      Microvasc Res

      Volume: 80(2) Pages: 179-87

    • Related Report
      2011 Final Research Report
  • [Journal Article] Role of endothelial cell-selective adhesion molecule in hematogeneous metastasis2010

    • Author(s)
      Cangara HM, Ishida T, Hara T, Sun L, Toh T, Rikitake Y, Kundu RK, Quertermous T, Hirata K, Hayashi Y
    • Journal Title

      Microvasc Res

      Volume: 80(1) Pages: 133-41

    • Related Report
      2011 Final Research Report
  • [Journal Article] Interaction of endothelial cell-selective adhesion molecule and MAGI-1 promotes mature cell-cell adhesion via activation of RhoA2010

    • Author(s)
      Kimura R, Ishida T, Kuriyama M, Hirata K, Hayashi Y
    • Journal Title

      Genes Cells

      Volume: 15(4) Pages: 385-396

    • Related Report
      2011 Final Research Report
  • [Journal Article] Pitavastatin decreases expression of endothelial lipase both in vitro and in vivo2010

    • Author(s)
      Kojima Y, Ishida T, Sun L, Yasuda T, Toh T, Rikitake Y, Fukuda A, Kume N, Koshiyama H, Taniguchi A, Hirata K
    • Journal Title

      Cardiovasc Res

      Volume: 87(2) Pages: 385-93

    • Related Report
      2011 Final Research Report
  • [Journal Article] 脂質リポ蛋白の検査血管内皮リパーゼ2010

    • Author(s)
      安田知行、石田達郎
    • Journal Title

      Medical Technology

      Volume: 38 Pages: 1361-1365

    • Related Report
      2011 Final Research Report
  • [Journal Article] HDL代謝における血管内皮リパーゼの役割と治療への応用2010

    • Author(s)
      石田達郎、平田健一
    • Journal Title

      医学のあゆみ

      Volume: 234 Pages: 7-8

    • Related Report
      2011 Final Research Report
  • [Journal Article] Update on the role of endothelial lipase in HDL metabolism, reverse cholesterol transport, and atherosclerosis.2010

    • Author(s)
      Yasuda T, Ishida T, et al.
    • Journal Title

      Circ J.

      Volume: 74 Pages: 2263-2270

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pitavastatin decreases expression of endothelial lipase both in vitro and in vivo.2010

    • Author(s)
      Kojima Y, Ishida T, et al.
    • Journal Title

      Cardiovasc Res

      Volume: 15 Pages: 385-393

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pitavastatin decreases expression of endothelial lipase both in vitro and in vivo.2010

    • Author(s)
      Kojima Y, et al.
    • Journal Title

      Cardiovasc Res (In press, 掲載確定)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article]2010

    • Author(s)
      石田達郎
    • Journal Title

      Annual Review糖尿病・代謝・内分泌2010(中外医学社)

      Pages: 152-159

    • Related Report
      2009 Annual Research Report
  • [Journal Article] Role of endothelial lipase in plasma HDL levels in a murine model of hypertriglyceridemia.2009

    • Author(s)
      Tanaka H, et al.
    • Journal Title

      J Atheroscler Thromb 16

      Pages: 327-338

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] HDLの異化の制御のCardiovascular Riskにおける役割を考える2009

    • Author(s)
      石田達郎
    • Journal Title

      Progress in Medicine. 5

      Pages: 39-46

    • Related Report
      2009 Annual Research Report
  • [Presentation] ESTABLISHMENT OF A NOVEL, HIGH-SENSITIVE ELISA SYSTEM FOR HUMAN ENDOTHELIAL LIPASE2012

    • Author(s)
      Ishida T, et al
    • Organizer
      HDL Satellite symposium 2012
    • Place of Presentation
      Cairns, Australia
    • Year and Date
      2012-03-30
    • Related Report
      2011 Annual Research Report
  • [Presentation] Plasma mass and activity of endothelial lipase are associated with coronary risk factors in humans2012

    • Author(s)
      Ishida T, Mori T, Sun L, Yasuda T, Hirata K
    • Organizer
      The XVI International Symposium on Atherosclerosis(ISA2012)
    • Place of Presentation
      Sydney, Australia. Workshop, Oral
    • Year and Date
      2012-03-27
    • Related Report
      2011 Final Research Report
  • [Presentation] Cardiac endothelial lipase expression is augmented in the early stage of heart failure2012

    • Author(s)
      Nakajima H, Ishida T, Sasaki M, Kondo K, Mori K, Hasokawa M, Haraguchi Y, Yasuda T, Kobayashi S, Hirata K
    • Organizer
      The XVI International Symposium on Atherosclerosis(ISA2012)
    • Place of Presentation
      Sydney, Australia. Poster
    • Year and Date
      2012-03-27
    • Related Report
      2011 Final Research Report
  • [Presentation] Plasma mass and activity of endothelial lipase are associated with coronary risk factors in humans2012

    • Author(s)
      Ishida T, et al
    • Organizer
      The XVI International Symposium on Atherosclerosis
    • Place of Presentation
      Sydney, Australia
    • Year and Date
      2012-03-27
    • Related Report
      2011 Annual Research Report
  • [Presentation] Cardiac endothelial lipase expression is augmented in a murine model of heart failure2012

    • Author(s)
      Nakajima H, et al
    • Organizer
      第76回日本循環器内会総会・学術集会
    • Place of Presentation
      Sydney, Austraria
    • Year and Date
      2012-03-26
    • Related Report
      2011 Annual Research Report
  • [Presentation] Cardiac endothelial lipase expression is augmented in a murine model of heart failure2012

    • Author(s)
      Nakajima H, Ishida T, Monguchi T, Sasaki M, Kondo K, Mori K, Hasokawa M, Haraguchi Y, Sun L, Yasuda T, Shinohara M, Toh R, Kobayashi S, Hirata K
    • Organizer
      第76回日本循環器学会学術集会
    • Place of Presentation
      福岡
    • Year and Date
      2012-03-17
    • Related Report
      2011 Final Research Report
  • [Presentation] Cardiac endothelial lipase expression is augmented in a murine model of heart failure2012

    • Author(s)
      Nakajima H, et al
    • Organizer
      第76回日本循環器内会総会・学術集会
    • Place of Presentation
      福岡
    • Year and Date
      2012-03-17
    • Related Report
      2011 Annual Research Report
  • [Presentation] Establishment of a novel, high-sensitive ELISA system for human endothelial lipase2012

    • Author(s)
      Ishida, T, Miyashita, K, Kinoshita, N, Seito, S, Hirata K, Nakajima K.
    • Organizer
      HDL Satellite symposium 2012
    • Place of Presentation
      Cairns, Australia
    • Related Report
      2011 Final Research Report
  • [Presentation] 糖尿病性動脈硬化における脂質異常の関与2011

    • Author(s)
      石田達郎, 他
    • Organizer
      第26回日本糖尿病合併症学会総会
    • Place of Presentation
      大宮
    • Year and Date
      2011-10-14
    • Related Report
      2011 Annual Research Report
  • [Presentation] Increased expression of endothelial lipase in a murine model of heart failure2011

    • Author(s)
      Nakajima H, et al
    • Organizer
      第43回日本動脈硬化学会総会・学術集会
    • Place of Presentation
      札幌
    • Year and Date
      2011-07-16
    • Related Report
      2011 Annual Research Report
  • [Presentation] Role of endothelial lipase in HDL metabolism and atherosclerosis in humans2011

    • Author(s)
      Ishida T, Toh R, Sun L, Yasuda T, Hirata K
    • Organizer
      79th European Atherosclerosis Society Congress
    • Place of Presentation
      Gothenburg, Sweden
    • Year and Date
      2011-06-28
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] Serum myeloperoxidase/paraoxonase 1 ratio is an independent predictor for repeat revascularization after percutaneous coronary intervention2010

    • Author(s)
      Haraguchi Y, Toh R, Ishida T, Hirata K
    • Organizer
      Scientific Sessions 2010 American Heart Association
    • Place of Presentation
      Chicago, USA
    • Year and Date
      2010-11-17
    • Related Report
      2011 Final Research Report
  • [Presentation] Plasma EL activity is a regulator of plasma HDL-cholesterol level and a target for HDL-raising therapies.2010

    • Author(s)
      Ishida T, Sun L, et al.
    • Organizer
      日本動脈硬化学会総会
    • Place of Presentation
      長良川国際会議場(岐阜県)
    • Year and Date
      2010-07-16
    • Related Report
      2010 Annual Research Report
  • [Presentation] Plasma EL activity is inversely correlated with the HDL-cholesterol level in humans2010

    • Author(s)
      Sun L, Ishida T, Toh R, Hirata K
    • Organizer
      第74回日本循環器学会総会・学術集会
    • Place of Presentation
      京都
    • Year and Date
      2010-03-05
    • Related Report
      2011 Final Research Report
  • [Presentation] Plasma EL activity is inversely correlated with the HDL-cholesterol level in humans2010

    • Author(s)
      Sun L, et al.
    • Organizer
      第74回 日本循環器学会総会・学術集会
    • Place of Presentation
      国立京都国際会館(京都府)
    • Year and Date
      2010-03-05
    • Related Report
      2009 Annual Research Report
  • [Presentation] Inactivation of endothelial lipase increases anti-inflammatory HDL particles2009

    • Author(s)
      Hara T, Ishida T, Kojima K, Hirata K
    • Organizer
      Scientific Sessions 2009 American Heart Association
    • Place of Presentation
      Orlando, FL, USA
    • Year and Date
      2009-11-17
    • Related Report
      2011 Final Research Report
  • [Presentation] Inactivation of endothelial lipase increases anti-inflammatory HDL particles.2009

    • Author(s)
      Hara T, et al.
    • Organizer
      Scientific Sessions 2009 American Heart Association.
    • Place of Presentation
      Orlando, FL,米国
    • Year and Date
      2009-11-17
    • Related Report
      2009 Annual Research Report
  • [Presentation] Inhibition of endothelial lipase can raise anti-atherogenic HDL particles2009

    • Author(s)
      石田達郎、安田知行、福田亨、平田健一
    • Organizer
      第41回日本動脈硬化学会総会.学術集会
    • Place of Presentation
      下関
    • Year and Date
      2009-07-17
    • Related Report
      2011 Final Research Report
  • [Presentation] Inhibition of endothelial lipase can raise anti-atherogenic HDL particles2009

    • Author(s)
      石田達郎
    • Organizer
      第41回日本動脈硬化学会総会・学術集会
    • Place of Presentation
      海峡メッセ下関(山口県)
    • Year and Date
      2009-07-17
    • Related Report
      2009 Annual Research Report
  • [Book] 血管内皮リパーゼの血中濃度と活性が血清HDL. Cと冠動脈硬化に及ぼす影響の検討.循環医学研究年報第4集2012

    • Author(s)
      石田達郎
    • Related Report
      2011 Final Research Report
  • [Book] 血管内皮リパーゼの臨床的意義. Annual Review糖尿病・代謝・内分泌20102010

    • Author(s)
      石田達郎、平田健一
    • Publisher
      中外医学社
    • Related Report
      2011 Final Research Report
  • [Book] 血管内皮リパーゼの臨床的意義2010

    • Author(s)
      石田達郎、平田健一
    • Total Pages
      8
    • Publisher
      中外医学社
    • Related Report
      2010 Annual Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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