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

• Project/Area Number: 21590897
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Kobe 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: ¥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.

Research Products

• [Journal Article] The Effect of Poloxamer 407 on the Functional Properties of HDL In Mice (2012)
  • Author(s): Yasuda T, Johnston TP, Shinohara M, Inoue M, Ishida T
  • Journal Title: Pharm Pharmacol Volume: 64(5) Pages: 677-87
• [Journal Article] Endothelial lipase mediates hdl levels in normal and hyperlipidemic rabbits (2012)
  • 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
• [Journal Article] FGD5 Mediates Pro-angiogenic Activity of Vascular Endothelial Growth Factor in Human Vascular Endothelial Cells (2012)
  • 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
• [Journal Article] The Effect of Poloxamer 407 on the Functional Properties of HDL In Mice (2012)
  • Author(s): Yasuda T., et al
  • Journal Title: J Pharm Pharmacol Volume: (In press)(掲載確定)(未定)
  • Peer Reviewed
• [Journal Article] Endothelial Lipase Mediates HDL Levels in Normal and Hyperlipidemic Rabbits (2012)
  • Author(s): Zhang J, et al
  • Journal Title: J Atheroscler Thromb Volume: (In press)(掲載確定)
  • Peer Reviewed
• [Journal Article] FGD5 Mediates Pro-angiogenic Activity of Vascular Endothelial Growth Factor in Human Vascular Endothelial Cells (2012)
  • Author(s): Kurogane Y, et al
  • Journal Title: Arterioscler Thromb Vasc Biol Volume: 32 Pages: 988-996
  • Peer Reviewed
• [Journal Article] Orally Administered Eicosapentaenoic Acid Induces Rapid Regression of Atherosclerosis Via Modulating the Phenotype of Dendritic Cells in LDL Receptor-Deficient Mice (2011)
  • 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
• [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
• [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, Kojima Y, Tanaka H, Yasuda T, Shinohara M, Toh R, Hirata K
  • Journal Title: J. Lipid Res Volume: 52(1) Pages: 57-67
• [Journal Article] Orally Administered Eicosapentaenoic Acid Induces Rapid Regression of Atherosclerosis Via Modulating the Phenotype of Dendritic Cells in LDL Receptor-Deficient Mice (2011)
  • Author(s): Nakajima K, et al
  • Journal Title: Arterioscler Thromb Vase Biol Volume: 31 Pages: 1963-72
  • 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
  • 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 functions (2010)
  • 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
• [Journal Article] Update on the role of endothelial lipase in HDL metabolism, reverse cholesterol transport, and atherosclerosis (2010)
  • Author(s): Yasuda T, Ishida T, Rader DJ
  • Journal Title: Circ J Volume: 74(11) Pages: 2263-70
• [Journal Article] Endothelial cell-selective adhesion molecule modulates atherosclerosis through plaque angiogenesis and monocyteendothelial interaction (2010)
  • 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
• [Journal Article] Role of endothelial cell-selective adhesion molecule in hematogeneous metastasis (2010)
  • 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
• [Journal Article] Interaction of endothelial cell-selective adhesion molecule and MAGI-1 promotes mature cell-cell adhesion via activation of RhoA (2010)
  • Author(s): Kimura R, Ishida T, Kuriyama M, Hirata K, Hayashi Y
  • Journal Title: Genes Cells Volume: 15(4) Pages: 385-396
• [Journal Article] Pitavastatin decreases expression of endothelial lipase both in vitro and in vivo (2010)
  • 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
• [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
• [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
• [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
  • 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
  • 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)
  • 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
• [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
  • 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
• [Presentation] ESTABLISHMENT OF A NOVEL, HIGH-SENSITIVE ELISA SYSTEM FOR HUMAN ENDOTHELIAL LIPASE (2012)
  • Author(s): Ishida T, et al
  • Organizer: HDL Satellite symposium 2012
  • Place of Presentation: Cairns, Australia
  • Year and Date: 2012-03-30
• [Presentation] Plasma mass and activity of endothelial lipase are associated with coronary risk factors in humans (2012)
  • 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
• [Presentation] Cardiac endothelial lipase expression is augmented in the early stage of heart failure (2012)
  • 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
• [Presentation] Plasma mass and activity of endothelial lipase are associated with coronary risk factors in humans (2012)
  • Author(s): Ishida T, et al
  • Organizer: The XVI International Symposium on Atherosclerosis
  • Place of Presentation: Sydney, Australia
  • Year and Date: 2012-03-27
• [Presentation] Cardiac endothelial lipase expression is augmented in a murine model of heart failure (2012)
  • 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
• [Presentation] Cardiac endothelial lipase expression is augmented in a murine model of heart failure (2012)
  • 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
• [Presentation] Cardiac endothelial lipase expression is augmented in a murine model of heart failure (2012)
  • 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
• [Presentation] Establishment of a novel, high-sensitive ELISA system for human endothelial lipase (2012)
  • Author(s): Ishida, T, Miyashita, K, Kinoshita, N, Seito, S, Hirata K, Nakajima K.
  • Organizer: HDL Satellite symposium 2012
  • Place of Presentation: Cairns, Australia
• [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
• [Presentation] Increased expression of endothelial lipase in a murine model of heart failure (2011)
  • 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
• [Presentation] Role of endothelial lipase in HDL metabolism and atherosclerosis in humans (2011)
  • 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
• [Presentation] Serum myeloperoxidase/paraoxonase 1 ratio is an independent predictor for repeat revascularization after percutaneous coronary intervention (2010)
  • 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
• [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
• [Presentation] Plasma EL activity is inversely correlated with the HDL-cholesterol level in humans (2010)
  • 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
• [Presentation] Plasma EL activity is inversely correlated with the HDL-cholesterol level in humans (2010)
  • 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
• [Presentation] Inactivation of endothelial lipase increases anti-inflammatory HDL particles (2009)
  • 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
• [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
• [Presentation] Inhibition of endothelial lipase can raise anti-atherogenic HDL particles (2009)
  • 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
• [Presentation] Inhibition of endothelial lipase can raise anti-atherogenic HDL particles (2009)
  • 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
• [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
• [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2010 (2010)
  • Author(s): 石田達郎、平田健一
  • Publisher: 中外医学社
• [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