Role of endothelial lipase in anti-inflammatory properties of high-density lipoprotein

• Project/Area Number: 22790705
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Circulatory organs internal medicine
• Research Institution: Kobe University
• Principal Investigator: HARA Tetsuya 神戸大学, 大学院・医学研究科, 医学研究員 (70547504)
• Research Collaborator: ISHIDA Tatsuro 神戸大学, 医学部附属病院, 准教授 (00379413) ; HIRATA Ken-ichi 神戸大学, 大学院・医学研究科, 教授 (20283880)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 炎症 / 動脈硬化 / 脂質代謝 / 血管内皮 / リパーゼ / 高比重リポ蛋白質 / 循環器 / 分子血管病態学 / 生活習慣病 / 高比重リポ蛋白

Research Abstract

Inhibition of endothelial lipase(EL) increases plasma high-density lipoprotein cholesterol(HDL-C) level. In this study, we assessed the functional quality of HDL isolated from EL-/-and WT mice. Anti-inflammatory functions of HDL, such as PON-1 or PAF-AH activities, inhibition of cytokine-induced VCAM-1 expression, inhibition of LDL oxidation, were similar between WT and EL-/-mice. In contrast, lipopolysaccharideneutralizing capacity of HDL was higher in EL-/-mice than in WT mice. Intravenous injection of HDL isolated from EL-/-mice improved the mortality in LPS-treated mice. Thus, EL inactivation increased plasma HDL particles with preserved anti-inflammatory and anti-atherosclerotic functions.

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: J Pharm Pharmacol Volume: 64 Pages: 677-87
• [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 Vase Biol Volume: 32 Pages: 988-996
  • 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, Kojima Y, Tanaka H, Yasuda T, Shinohara M, Toh R, Hirata K.
  • Journal Title: J. Lipid Res Volume: 52 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): Tetsuya Hara, et al.
  • Journal Title: Journal of lipid Research Volume: 52 Pages: 57-67
  • Peer Reviewed
• [Journal Article] Rader DJ. Update on the role of endothelial lipase in HDL metabolism, reverse cholesterol transport, and atherosclerosis (2010)
  • Author(s): Yasuda T, Ishida T
  • Journal Title: Circ J Volume: 74 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 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 Pages: 133-41
• [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 Pages: 385-93
• [Journal Article] Role of endothelial cell-selective adhesion molecule in hematogeneous metastasis (2010)
  • Author(s): Cangara HM, et al.
  • Journal Title: Microvasc Res. Volume: 80 Pages: 133-141
  • Peer Reviewed
• [Journal Article] Endothelial cell-selective adhesion molecule modulates atherosclerosis through plaque angiogenesis and monocyte-endothelial interaction. (2010)
  • Author(s): Inoue M, et al.
  • Journal Title: Microvasc Res. Volume: 80 Pages: 179-187
  • Peer Reviewed
• [Presentation] Establishment of a novel, highsensitive 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
  • Year and Date: 2012-03-30
• [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
  • 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
  • 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] 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
• [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