Targeting endothelial lipase as a novel therapeutic strategy for the treatment of atherosclerosis

2010 Fiscal Year Final Research Report

• Project/Area Number: 21790314
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Pathological medical chemistry
• Research Institution: University of Yamanashi
• Principal Investigator: KOIKE Tomonari University of Yamanashi, 大学院・医学工学総合研究部, 助教 (40432158)
• Project Period (FY): 2009 – 2010
• Keywords: 分子病態学 / 動脈硬化

Research Abstract

To establish a novel strategy for raising plasma HDL-cholesterol levels, we analyzed the functions of endothelial lipase (EL), a newly-identified HDL phospholipase, using rabbit models. We found that EL expression was increased in rabbits with low HDL-cholesterol levels. Inhibition of EL expression using EL specific antisense led to increased plasma HDL-cholesterol levels. These results indicate the therapeutic inhibition of EL activity may become a new mean to elevate plasma HDL levels.

Research Products

• [Journal Article] Human C-reactive protein enhances thrombus formation after neointimal balloon injury in transgenic rabbits. (2011)
  • Author(s): Matsuda S, Yamashita A, Sato Y, Kitajima S, Koike T, Sugita C, Moriguchi-Goto S, Hatakeyama K, Takahashi M, Koshimoto C, Matsuura Y, Iwakiri T, Chen Y.E, Fan J, Asada Y
  • Journal Title: J Thromb Haemost 9 Pages: 201-208
  • Peer Reviewed
• [Journal Article] High-fat diet without excess calories induces metabolic disorders and enhances atherosclerosis in rabbits. (2010)
  • Author(s): Waqar AB, Koike T, Yu Y, Inoue T, Aoki T, Liu E, Fan J
  • Journal Title: Atherosclerosis 213 Pages: 148-155
  • Peer Reviewed
• [Journal Article] Human C-reactive protein does not promote atherosclerosis in transgenic rabbits. (2009)
  • Author(s): Koike T, Kitajima S, Yu Y, Nishijima K, Zhang J, Ozaki Y, Morimoto M, Watanabe T, Bhakdi S, Asada Y, Chen Y.E, Fan, J
  • Journal Title: Circulation 120 Pages: 2088-2094
  • Peer Reviewed
• [Journal Article] Expression of human apoAII in transgenic rabbits leads to dyslipidemia: a new model for combined hyperlipidemia (2009)
  • Author(s): Koike T, Kitajima S, Yu Y, Li Y, Nishijima K, Liu E, Sun H, Waqar A.B., Shibata N, Inoue T, Wang Y, Zhang B, Kobayashi J, Morimoto M, Saku K, Watanabe T, Fan J
  • Journal Title: Arterioscler Thromb Vasc Biol 29 Pages: 2047-2053
  • Peer Reviewed
• [Presentation] Expression of Human ApoAII in Transgenic Rabbits Leads to Dyslipidemia -A New Model for Combined Hyperlipidemia. (2010)
  • Author(s): Koike T, Kitajima S, Yu Y, Nishijima K, Waqar AB, Inoue T, Wang Y, Bo Z, Kobayashi, J, Morimoto M, Saku K, Watanabe T, Fan J
  • Organizer: 第42回日本動脈硬化学会総会・学術集会
  • Place of Presentation: 岐阜市
  • Year and Date: 20100715-20100716
• [Presentation] Human C-reactive protein enhances thrombus formation in transgenic rabbits. (2010)
  • Author(s): Matsuda S, Kitajima S, Koike T, Fan J, Asada Y
  • Organizer: 第42回日本動脈硬化学会総会・学術集会
  • Place of Presentation: 岐阜市
  • Year and Date: 20100715-20100716
• [Presentation] 動脈硬化の発生におけるC反応性蛋白の役割:遺伝子改変ウサギ・モデルによる解析 (2010)
  • Author(s): 範江林, 小池智也, 北嶋修司, 浅田祐士郎, 渡辺照男
  • Organizer: 第99回日本病理学会総会
  • Place of Presentation: 新宿区
  • Year and Date: 20100427-20100429
• [Presentation] 実験的関節炎形成におけるC反応性蛋白の役割 (2010)
  • Author(s): 青木正, 小池智也, Waqar AB, Yu Y, 井上朋大, 柴田信光, 西島和俊, 北嶋修司, 能勢眞人, 範江林
  • Organizer: 第99回日本病理学会総会
  • Place of Presentation: 新宿区
  • Year and Date: 20100427-20100429
• [Presentation] 内皮リパーゼ特異的アンチセンスによる発現阻害効果とHDL代謝への影響 (2010)
  • Author(s): Yu Y, Koike T, Zhang X Zhang J, Fan J
  • Organizer: 第4回ウサギフォーラム
  • Place of Presentation: 秋田市
  • Year and Date: 2010-07-24
• [Presentation] Transgenic rabbits expressing Human C-reactive protein. (2009)
  • Author(s): Koike T, Kitajima S, Yu Y, Nishijima K, Zhang J, Ozaki Y, Morimoto M, Watanabe T, Asada Y, Chen E, Fan J
  • Organizer: 第41回日本動脈硬化学会総会・学術集会
  • Place of Presentation: 下関市
  • Year and Date: 20090717-20090718
• [Presentation] High-Fat-Diet-induced metabolic disorders enhances atherosclerosis. (2009)
  • Author(s): Waqar AB, Koike T, Yu Y, Shibata N, Inoue T, Aoki T, Fan J
  • Organizer: 第41回日本動脈硬化学会総会・学術集会
  • Place of Presentation: 下関市
  • Year and Date: 20090717-20090718
• [Presentation] Molecular cloning and characterization of rabbit endothelial lipase. (2009)
  • Author(s): Yu Y, Zhang J, Koike T, Ishida T, Hirata K, Chen E, Fan J
  • Organizer: 第41回日本動脈硬化学会総会・学術集会
  • Place of Presentation: 下関市
  • Year and Date: 20090717-20090718
• [Presentation] Transgenic rabbits expressing human C-reactive protein. (2009)
  • Author(s): Koike T, Yu Y, Kitajima S, Zhang J, Bhakdi S, Chen E.Y., Fan J
  • Organizer: 3rd International Meeting on Rabbit Biotechnology
  • Place of Presentation: Xian, China
  • Year and Date: 20090604-20090605
• [Presentation] Immunoreactivity of neuropeptides in hypothalamus of the transgenic rabbits using immunohisotchemical staining. (2009)
  • Author(s): Morimoto M, Kitajima S, Nishijima K, Koike T, Fan J
  • Organizer: 3rd International Meeting on Rabbit Biotechnology
  • Place of Presentation: Xian, China
  • Year and Date: 20090604-20090605
• [Presentation] Transgenic Rabbits Expressing human C-reactive Protein. (2009)
  • Author(s): Koike T, Yu Y, Kitajima S, Zhang J, Bhakdi S, Chen YE, Fan J
  • Organizer: Arteriosclerosis, Thrombosis and Vascular Biology Annual Conference 2009
  • Place of Presentation: Washington DC, USA
  • Year and Date: 20090429-20090501
• [Remarks] ホームページ等
  • URL: http://www.med.yamanashi.ac.jp/clinical_basic/pathol01/