Role of endothelial lipase in serum HDL cholesterol level and life style

2010 Fiscal Year Final Research Report

• Project/Area Number: 20590825
• 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: ISHIKAWA Yuichi Kobe University, 大学院・保健学研究科, 名誉教授 (90159707)
• Co-Investigator(Kenkyū-buntansha): HIRATA Kenーichi 神戸大学, 大学院・医学研究科, 教授 (20283880) ; ISHIDA Tatsuro 神戸大学, 医学部附属病院, 准教授 (00379413)
• Project Period (FY): 2008 – 2010
• Keywords: 脂質代謝 / 高比重リポ蛋白 / 血管内皮リパーゼ / 動脈硬化 / 生活習慣病 / 循環器

Research Abstract

High-density lipoprotein cholesterol (HDL-C) is a negative risk factor for atherosclerosis. Endothelial lipase (EL) is a regulator of plasma HDL levels. This study was undertaken to clarify the role of EL in serum HDL-C level and life style. Serum EL protein levels were inversely correlated with serum HDL-C levels. Pitavastatin decreased EL levels and increased HDL levels. Serum EL activity was inversely correlated with serum HDL-C levels, and higher in patients with coronary artery disease compared to control subjects. In animal models of low HDL levels, inhibition of EL resulted in a raise in plasma HDL-C levels. Thus, EL is a determinant of plasma HDL levels in humans, and EL inhibition would be useful for HDL-raising therapy.

Research Products

• [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 KI
  • Journal Title: J.Lipid Res. 52(1) Pages: 57-67
• [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. 74(11) Pages: 2263-2270
• [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 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。特集:コレステロール吸収?リポ蛋白代謝研究から新たな脂質異常症治療へ (2010)
  • Author(s): 石田達郎、平田健一
  • Journal Title: 医学のあゆみ 234 Pages: 7-8
• [Journal Article] Endothelial cell-selective adhesion molecule modulates atherosclerosis through plaque angiogenesis and monocyte-endothelial 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. 80(2) Pages: 179-187
• [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. 80(1) Pages: 133-141
• [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. 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 87(2) Pages: 385-393
• [Journal Article] The Adhesion Molecule ESAM1 is A Novel Hematopoietic Stem Cell Marker. (2009)
  • Author(s): Ooi AG, Karsunky H, Majeti R, Butz S, Vestweber D, Ishida T, Quertermous T, Weissman IL, Forsberg EC.
  • Journal Title: Stem Cells. 27(3) Pages: 653-661
• [Journal Article] RAGE mediates oxidized LDL-induced pro-inflammatory actions and atherosclerosis in non-diabetic LDL receptor-deficient mice. (2009)
  • Author(s): Sun L, Ishida T, Yasuda T, Kuriyama M, Kojima Y, Yamamoto Y, Yamamoto H, Ishibashi S, Hirata K, Hayashi K.
  • Journal Title: Cardiovasc Res. 82(2) Pages: 371-381
• [Journal Article] Targeted inactivation of endothelial lipase attenuates lung allergic inflammation through raising plasma HDL level and inhibiting eosinophil infiltration. (2009)
  • Author(s): Otera H, Ishida T, Nishiuma T, Kobayashi K, Kotani K, Yasuda T, Kundu RK, Quertermous T, Hirata K, Nishimura Y.
  • Journal Title: Am J Physiol-Lung Cell Mol Physiol 296(4) Pages: L594-602
• [Journal Article] Endothelial cell-selective adhesion molecule regulates albuminuria in diabetic nephropathy. (2009)
  • Author(s): Hara T, Ishida T, Cangara HM, Hirata K
  • Journal Title: Microvasc Res. 77(3) Pages: 348-355
• [Journal Article] Role of endothelial lipase in low HDL levels in a murine model of hypertriglyceridemia. (2009)
  • Author(s): Tanaka H, Ishida T, Johnston TP, Kojima Y, Yasuda T, Kundu RK, Quertermous T, Ishikawa Y, Hirata K
  • Journal Title: J Atheroscler Thromb. 16(4) Pages: 327-338
• [Journal Article] HDLの異化の制御のCardiovascular Riskにおける役割を考える. HDLを再考する (2009)
  • Author(s): 石田達郎、平田健一
  • Journal Title: Progress in Medicine 5 Pages: 39-46
• [Journal Article] Putative role of endothelial lipase in dialysis patients with hypoalbuminemia and inflammation. (2008)
  • Author(s): Fujii H, Fukuda A, Tanaka M, Kojima Y, Ishida T, Hirata K, Fukagawa M.
  • Journal Title: Am J Nephrol. 28(6) Pages: 974-981
• [Presentation] Hypertriglycemia lowers plasma HDL-C levels and generates “dysfunctional HDL" in mice. (2011)
  • Author(s): Yasuda T, Ishida T, Johnston TP, Inoue M, Hirata K
  • Organizer: 第75回日本循環器学会総会・学術集会
  • Year and Date: 2011-03-19
• [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, Toh R, Hirata K
  • Organizer: 日本動脈硬化学会総会
  • Place of Presentation: 長良川会議場 岐阜
  • Year and Date: 2010-07-15
• [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(JCS2010)
  • Place of Presentation: 京都
  • 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.
  • 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] Inactivation of endothelial lipase increases “good cholesterol". (2009)
  • Author(s): Hara T, Ishida T, Kojima Y, Hirata K
  • Organizer: 第73回 日本循環器学会総会・学術集会(JCS2009)
  • Place of Presentation: 大阪
  • Year and Date: 2009-03-22
• [Presentation] Targetd inactivation of receptor for advanced glycation products reduced oxidative LDL-induced inflammation and atherosclerosis in non-diabetic LDL receptor-/-mice. (2008)
  • Author(s): Sun L, Ishida T, Kuriyama M, Yasuda T, Hara T, Hirata K, Hayashi Y.
  • Organizer: American Heart Association Scientific Sessions 2008.
  • Place of Presentation: New Orleans, LA.
  • Year and Date: 2008-11-11
• [Presentation] Targeted Deletion Of Endothelial Lipase Protects Against Allergic Asthma Through Raising Plasma HDL Level And Attenuating Eosinophil Infiltration. (2008)
  • Author(s): Ishida T, Otera H, Yasuda T, Nishimura Y, Hirata K
  • Organizer: American Heart Association Scientific Sessions 2008.
  • Place of Presentation: New Orleans, LA.
  • Year and Date: 2008-11-10
• [Presentation] Effect of pitavastatin on serum concentrations of endothelial lipase and high-density lipoprotein cholesterol in humans. (2008)
  • Author(s): Sun L, Ishida T, Kojima Y, Yasuda T, Fukuda A, Kureha F, Hirata K
  • Organizer: American Heart Association Scientific Sessions 2008.
  • Place of Presentation: New Orleans, LA.
  • Year and Date: 2008-11-10
• [Presentation] 家兎における血管内皮リパーゼの過剰発現が血清脂質に及ぼす影響 (2008)
  • Author(s): 石田達郎、安田知行、平田健一
  • Organizer: 第3回ウサギフォーラム
  • Place of Presentation: 神戸
  • Year and Date: 2008-07-26
• [Presentation] Role of endothelial lipase in the HDL-raising effects of statins. (2008)
  • Author(s): 石田達郎、安田知行、福田亨、平田健一
  • Organizer: 第40回日本動脈硬化学会総会・学術集会
  • Place of Presentation: つくば
  • Year and Date: 2008-07-11
• [Presentation] 血管内皮リパーゼの血中濃度と血清HDL値との関係 (2008)
  • Author(s): 石田達郎、福田亨、児島陽子、安田知行、平田健一
  • Organizer: 第105回 内科学会講演会
  • Place of Presentation: 東京
  • Year and Date: 2008-04-11
• [Book] 循環器ストレス学 2010. 第1版(編:横山光宏、井上信孝)(脂質異常症、メタボリックシンドロームとストレス応答) (2010)
  • Author(s): 乙井一典、石田達郎、平田健一
  • Total Pages: 282-293
  • Publisher: 南山堂
• [Book] Annual Review糖尿病・代謝・内分泌2010.(編:寺内康夫、伊藤裕、石橋俊)(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: 152-159
  • Publisher: 中外医学社
• [Remarks] ホームページ等なし