Role of endothelial lpase in metabolic syndrome

• Project/Area Number: 19590863
• 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: HIRATA Ken-ich Kobe University, 大学院医学研究科, 教授 (20283880)
• Co-Investigator(Kenkyū-buntansha): ISHIDA Tatsuro 神戸大学, 大学院医学研究科, 助教 (00379413)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2007: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: (1)脂質 / (2)糖尿病 / (3)蛋白質 / (4)循環器・高血圧 / (5)臨床 / 脂質 / 糖尿病 / 蛋白質 / 循環器・高血圧 / 臨床

Research Abstract

本研究では、血管内皮リパーゼ(EL)がメタボリックシンドロームにおける低HDL血症にはたす役割を検討した。インスリン抵抗性のモデルであるdb/dbマウスでは肝臓におけるEL発現が増加しており低HDL-C値と脂肪肝の原因となることが示された。また、ヒト血中EL濃度は血清HDL-C値と有意に逆相関したが、LDL-C、中性脂肪値とは相関関係はなかった。ヒトでELを不活性化するとHDLのみが選択的に上昇することが示唆された。

Research Products

• [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: 371-81
  • Peer Reviewed
• [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: American Journal of Physiology-Lung Cellular and Molecular Physiology 296(4)
  • Peer Reviewed
• [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, et al.
  • Journal Title: Am J Physiol Lung Coll Mol Physiol (In press)
  • Peer Reviewed
• [Journal Article] RAGE mediates oxidized LDL-induced pro-inflammatory effects and atherosclerosis in non-diabetic LDL receptor-deficient mice (2009)
  • Author(s): Sun L, et al.
  • Journal Title: Cardiovascular Research (In press)
  • Peer Reviewed
• [Journal Article] Role of endothelial lipase in plasma HDL levels in a murine model of hypertriglyceridemia (2009)
  • Author(s): Tanaka T, et al.
  • Journal Title: J Atherosclerosis and Thrombosis (In press)
  • Peer Reviewed
• [Journal Article] Endothelial cell-selective adhesion molecule regulates albuminuria in diabetic nephropalhy (2009)
  • Author(s): Hara T, et al.
  • Journal Title: Microvascular Research (In press)
  • Peer Reviewed
• [Journal Article] Putative role of endothelial lipase in dialysis patients with hypoalbuminemia and inflammation (2008)
  • Author(s): ujii H, Fukuda A, Tanaka M, Kojima Y, Ishida T, Hirata K, Fukagawa M
  • Journal Title: Am J Nephrol 28(6) Pages: 974-81
  • Peer Reviewed
• [Journal Article] Endothelial lipase is increased by inflammation and promotes LDL uptake in macrophages (2007)
  • Author(s): Yasuda T,Hirata K, Ishida T, Kojima Y, Tanaka H, Okada T, Quertermous T, Yokoyama M
  • Journal Title: JAtheroscler Thromb 14(4) Pages: 192-201
  • NAID: 10022606886
  • Peer Reviewed
• [Journal Article] Endothelial lipase gene polymorphism is associated with acute myocardial infarction, independently of high-density lipoprotein-cholesterol levels (2007)
  • Author(s): Shimizu M, Kanazawa K, Hirata K, Ishida T, Hiraoka E, Matsuda Y, Iwai C, Miyamoto Y, Hashimoto M, Kajiya T, Akita H, Yokoyama M
  • Journal Title: Circ J 71(6) Pages: 842-6
  • NAID: 110006273822
  • Peer Reviewed
• [Journal Article] Angiopoietin-like protein3 regulates plasma HDL cholesterol through suppression of endothelial lipase (2007)
  • Author(s): Shimamura M, Matsuda M, Yasumo H, Okazaki M, Fujimoto K, Kono K, Shimizugawa T, Ando Y, Koishi R, Kohama T, Sakai N, Kotani K, Komuro R, Ishida T, Hirata K, Yamashita S, Furukawa H, Shimomura I
  • Journal Title: Arterioscler Thromb Vasc Biol 27(2) Pages: 366-72
  • Peer Reviewed
• [Journal Article] Endothelial lipase is increased by inflammation and promotes LDL uptake in macrophages. (2007)
  • Author(s): Yasuda T, et. al.
  • Journal Title: J Atheroscler Thromb. 14(4) Pages: 192-201
  • Peer Reviewed
• [Journal Article] Endothelial lipase gene polymorphism is associated whti acute myocardial infarction, independently of high-density liporotein-cholesterol levels. (2007)
  • Author(s): Shimizu M, et. al.
  • Journal Title: Circ J. 71(6) Pages: 842-846
  • Peer Reviewed
• [Journal Article] A specific role for eNOS-derived reactive oxygen species in atherosclerosis progression. (2007)
  • Author(s): Takaya T, et. al.
  • Journal Title: Arterioscler Thromb Vasc Biol 27(7) Pages: 1632-1637
  • Peer Reviewed
• [Journal Article] Endothelial cell-selective adhesion molecule regulates albuminuria in diabetic nephropathy.
  • Author(s): Hara T, Ishida T, Cangara HM, Hirata K
  • Journal Title: Microvasc Res Pages: 0-0
  • Peer Reviewed
• [Journal Article] Role of endothelial lipase in low HDL levels in a murine model of hypertriglyceridemia.
  • Author(s): Tanaka H, Ishida T, Johnston TP, Kojima Y, Yasuda T, Kundu RK, Quertermous T,Hirata K
  • Journal Title: J Atheroscler Thromb. Pages: 0-0
  • Peer Reviewed
• [Presentation] Inhibition of endothelial lipase increases good cholesterol (2009)
  • Author(s): 原 哲也, 他
  • Organizer: 第73回日本循環器学会総会
  • 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] Effect of pitavastatin on serum concentrations of endothelial lipase and high-density lipoprotein cholesterol in humans (2008)
  • Author(s): Sun Li, Tatsuro Ishida, Yoko Kojima, Tomoyuki Yasuda, Akira Fukuda, Fumie Kureha, Ken-ichi Hirata
  • Organizer: American Heart Association Scientific Sessions 2008
  • Place of Presentation: New Orleans, LA
  • Year and Date: 2008-11-10
• [Presentation] Targeted Deletion Of Endothelial Lipase Protects Against Allergic Asthma Through Raising Plasma HDL Level And Attenuating Eosinophil Infiltration (2008)
  • Author(s): Tatsuro Ishida, Hiroshi Otera, Tomoyuki Yasuda, Yoshihiro Nishimura, Ken-ichi Hirata
  • 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 Li, et al.
  • Organizer: American Heart Association Scientific Sessions2008
  • Place of Presentation: New Orleans, LA, USA
  • Year and Date: 2008-11-10
• [Presentation] Targetd inactivation of receptor for advanced glycation products reducedoxiclative LDL-induced inflammation and alhcrosclerosis in non-diabetic LDL receptor-/- mice. (2008)
  • Author(s): Sun Li, et al.
  • Organizer: American Heart Association Scientific Sessions2008
  • Place of Presentation: New Orleans, LA, USA
  • Year and Date: 2008-11-10
• [Presentation] Role of endothelial cell-selective adhesion molecule in the progression of atherosclerosis. (2008)
  • Author(s): Inoue M, et al.
  • Organizer: American Heart Association Scientific Sessions2008
  • Place of Presentation: New Orleans, LA, USA
  • Year and Date: 2008-11-10
• [Presentation] Targeted Deletion Of Endothelial Lipase Protects Against Allergic Asthma Through Raising Plasma HDL Level And Attenuating EosinophilInfiltration. (2008)
  • Author(s): Ishida T, et al.
  • Organizer: American Heart Association Scientific Sessions2008
  • Place of Presentation: New Orleans, LA, USA
  • 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, 他
  • 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] Role of endothelial lipase in the HDL-raising effects of statins (2008)
  • Author(s): 石田達郎, 他
  • 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: 2008-07-10
• [Presentation] 動脈硬化形成過程におけるendothelial cell-selective adhesion molecule (ESAM)の役割について (2008)
  • Author(s): 井上通彦, 他
  • 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: 2008-07-10
• [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回日本内科学会講演会
  • Place of Presentation: 東京
  • Year and Date: 2008-04-11
• [Presentation] 血管内皮リパーゼの血中濃没と血清HDL値との関係 (2008)
  • Author(s): 石田達郎, 他
  • Organizer: 第105回日本内科学会講演会
  • Place of Presentation: 東京
  • Year and Date: 2008-04-11
• [Presentation] RAGE Deficiency Inhibit the Atherosclerosis Progression in non diabetic Low-Density Lipoprotein Receptor Knockout Mice (2008)
  • Author(s): LiS, Ishida T, Kuriyama M, Yasuda T, Hara T, Hayashi Y, Hirata K
  • Organizer: 第72回 日本循環器学会総会・学術集会
  • Place of Presentation: 福岡
  • Year and Date: 2008-03-28
• [Presentation] Endothelial Lipase is a Key Molecule of Postprandial Hypertriglycemia in Mice (2008)
  • Author(s): Fukuda A, Ishida T, Yasuda T, Hirata K
  • Organizer: 第72回 日本循環器学会総会・学術集会(JCS2008)
  • Place of Presentation: 福岡
  • Year and Date: 2008-03-28
• [Presentation] Endothelial lipase selectively regulates HDL metabolism in rabbits (2008)
  • Author(s): Yasuda T, Ishida T, Okada T, Fukuda A, Hara T, Inoue M, Kureha F, Hirata K
  • Organizer: 第72回 日本循環器学会総会・学術集会(JCS2008)
  • Place of Presentation: 福岡
  • Year and Date: 2008-03-28
• [Presentation] Overexpression of endothelial lipase in the liver promotes the clearance of plasma lipids but accelerates liver steatosis in a mouse model of metabolic syndrome (2007)
  • Author(s): Yasuda T, Ishida T, Kojima Y, Tanaka H, Okada T, Fukuda A, Hara T, Inoue M,Hirata K
  • Organizer: American Heart Association Scientific Sessions 2007
  • Place of Presentation: Chicago, IL
  • Year and Date: 2007-11-10
• [Presentation] 炎症により発現したLDL受容体はマクロファージにおいて中性脂肪優位リポ蛋白の取り込みに重要である (2007)
  • Author(s): 安田知行、平田健一、石田達郎、福田亨
  • Organizer: 第39回日本動脈硬化学会総会?学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2007-07-13
• [Presentation] Targeted inactivation of endothelial lipase improves the low plasma HDL level associated with hypertriglyceridemia (2007)
  • Author(s): Ishida T, et. al.
  • Organizer: Satellite syposium on HDL and atherosclerosis, European Atherosclerosis Society 76th Congress The XVth Paavo Nurmi Symposium
  • Place of Presentation: Helsinki, Finland
  • Year and Date: 2007-06-08
• [Book] DATA UPDATE循環系 第4版「JELIS」 (2009)
  • Author(s): 石田達郎、平田健一
  • Publisher: 先端医学社
• [Book] 新・心臓病診療プラクティスシリーズ12 冠動脈疾患の病態に迫る「高LDLコレステロール血症/低HDLコレステロール血症の関与」 (2008)
  • Author(s): 石田達郎、平田健一
  • Publisher: .文光堂
• [Book] β遮断薬のすべて 第3版. 「β遮断薬の血管・血管内皮に対する作用」 (2008)
  • Author(s): 原哲也、石田達郎、平田健一
  • Publisher: 先端医学社
• [Book] 循環器疾患最新の治療2008-2009 「冠動脈疾患と抗血小板療法」 (2008)
  • Author(s): 石田達郎、横山光宏
  • Publisher: 南江堂