Identification of molecular mechanisms underlying the common pathogenesis of atherosclerosis and obesity

• Project/Area Number: 19390218
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Kumamoto University
• Principal Investigator: OIKE Yuichi Kumamoto University, 大学院・医学薬学研究部, 教授 (90312321)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000); Fiscal Year 2008: ¥8,580,000 (Direct Cost: ¥6,600,000、Indirect Cost: ¥1,980,000); Fiscal Year 2007: ¥10,010,000 (Direct Cost: ¥7,700,000、Indirect Cost: ¥2,310,000)
• Keywords: 動脈硬化 / 肥満 / アンジオポエチン様因子 / マクロファージ / 炎症

Research Abstract

ANGPTL2濃度は、健常人より糖尿病患者群で血中有意に高いこと、健常人及び糖尿病患者の両群で肥満(BMIもしくは内臓脂肪面積)の程度、炎症(血中CRP濃度)の程度、インスリン抵抗性の程度に比例して上昇することを見出し、ANGPTL2と肥満、動脈硬化性疾患の連関の可能性を見出した。さらにANGPTL2遺伝子改変マウスを用いた研究でAngptl2は、肥満病態でみられる脂肪組織の炎症、それに随伴する耐糖能異常、インスリン抵抗性の誘発因子であり、発現上昇抑制が治療標的になりうることを見出した。

Research Products

• [Journal Article] Resveratrol Prevents Ocular Inflammation in Endotoxin-Induced Uveitis via Inhibiting Oxidative Damage and Nuclear Factor-kB Activation (2009)
  • Author(s): Kubota S, Kurihara T, Mochimaru H, Satofuka S, Noda K, Ozawa Y, Oike Y, Ishida S, & Tsubota K.
  • Journal Title: Invest Ophthalmol Vis Sci in press
  • Peer Reviewed
• [Journal Article] Angptl 4 deficiency improves lipid metabolism, suppresses foam cell formation and protects against atherosclerosis (2009)
  • Author(s): Adachi H, Fujiwara Y, Kondo T, Nishikawa T, Ogawa R, Matsumura T, Ishii N, Nagai R, Miyata K, Tabata M, Motoshima H, Furukawa N, Tsuruzoe K, Kawashima J, Takeya M, Yamashita S, Koh GY, Nagy A, Suda T, Oike Y, & ArakiE.
  • Journal Title: Biochem Biophys Res Commun 379 Pages: 806-811
  • Peer Reviewed
• [Journal Article] Angptl 4 deficiency improves lipid metabolism, suppresses foam cell formation and protects against atherosclerosis. (2009)
  • Author(s): Adachi H., et al
  • Journal Title: Biochem Biophys Res Commun. 379 Pages: 806-811
  • Peer Reviewed
• [Journal Article] Resveratrol Prevents Ocular Inflammation in Endotoxin-Induced Uveitis via Inhibiting Oxidative Damage and Nuclear Factor-{kappa}B Activation. (2009)
  • Author(s): Kubota S., et al
  • Journal Title: Invest Ophthalmol Vis Sci. (in press)
  • Peer Reviewed
• [Journal Article] Hepatic AdiopoR2 signaling plays a protective role against progression of nonalcoholic steatohepatitis in mice (2008)
  • Author(s): Tomita K, Oike Y, Teratani T, Taguchi T, Noguchi M, Suzuki T, Mizutani A, Yokoyama H, Irie R, Sumimoto H, Takayanagi A, Miyashita K, Akao M, Tabata M, Tamiya G, Ohkura T, & Hibi T.
  • Journal Title: Hepatology 48 Pages: 458-473
  • Peer Reviewed
• [Journal Article] Inhibition of choroidal neovascularization with an anti-inflammatory carotenoid astaxanthin (2008)
  • Author(s): Izumi-Nagai K, Nagai N, Ohgami K, Satofuka S, Ozawa Y, Tsubota K, Ohno S, Oike Y, & Ishida S.
  • Journal Title: Invest Ophthalmol Vis Sci 49 Pages: 1679-1685
  • Peer Reviewed
• [Journal Article] Angiopoietin-related growth factor enhances blood flow via activation of the ERK1/2-eNOS-NO pathway in a mouse hind-limb ischemia model (2008)
  • Author(s): Urano T, Ito Y, Akao M, Sawa T, Miyata K, Tabata M, Morisada T, Hato T, Kadomatsu T, Yano T, Yasunaga K, Shibata R, Murohara T, Akaike T, Tanihara H, Suda T. & Oike Y.
  • Journal Title: Arterioscler Thromb Vasc Biol 28 Pages: 827-834
  • Peer Reviewed
• [Journal Article] The roleof angiopoietin-like proteins (Angptls) in angiogenesis and metabolism (2008)
  • Author(s): Hato T, Tabata M, & Oike Y.
  • Journal Title: Trends Cardiovasc Med 18 Pages: 6-14
  • Peer Reviewed
• [Journal Article] Hepatic AdiopoR2 signaling plays a protective role against progression of nonalcoholic steatohepatitis in mice. (2008)
  • Author(s): Tomita K., et al
  • Journal Title: Hepatology 48 Pages: 458-473
  • Peer Reviewed
• [Journal Article] Angiopoietin-related growth factor enhances blood flow via activation of the ERK1/2-eNOS-NO pathway in a mouse hind-limbischemia model. (2008)
  • Author(s): Urano T., et al
  • Journal Title: Arterioscler Thromb Vase Biol. 28 Pages: 827-834
  • Peer Reviewed
• [Journal Article] Inhibition of choroidal neovascularization with an anti-inflammatory carotenoid astaxanthin. (2008)
  • Author(s): Izumi-Nagai K., et al
  • Journal Title: Invest Ophthalmol Vis Sci. 49 Pages: 1679-1685
  • Peer Reviewed
• [Journal Article] The role of angiopoietin-like proteins (Angptls)in angiogenesis and metabolism. (2008)
  • Author(s): Hato T., et al
  • Journal Title: Trends Cardiovasc Med. 18 Pages: 6-14
  • Peer Reviewed
• [Journal Article] Angiopoietin-related growth factor enhances blood flow via activation of the ERK1/2-eNOS-NO pathway in a mouse hind-limb ischemia model. (2008)
  • Author(s): Urano, T., et. al.
  • Journal Title: Arterioscler Thromb Vasc Biol (in Press)
  • Peer Reviewed
• [Journal Article] The role of angiopoietin-like proteins (Angptls) in angiogenesis and metabolism. (2008)
  • Author(s): Hato, T., et. al.
  • Journal Title: Trends Cardiovasc Med. 18 Pages: 6-14
  • Peer Reviewed
• [Journal Article] Angiopoietin-related growth factor (AGF) suppresses gluconeogenesis through the Akt/Fox01-dependent pathway in hepatocytes (2007)
  • Author(s): Kitazawa M, Ohizumi Y, Oike Y, Hashinuma T, & Hashimoto S.
  • Journal Title: J Pharmacol Exp Ther 323 Pages: 787-793
  • Peer Reviewed
• [Journal Article] AngiogenicRole of LYVE-1-positive Macrophagesin Adipose Tissue (2007)
  • Author(s): Cho CH, Jun Koh Y, Han J, Sung HK, Jong Lee H, Morisada T, Schwendener RA, Brekken RA, Kang G, Oike Y, Choi TS, Suda T, Yoo OJ, & Koh, GY.
  • Journal Title: Circ Res 100 Pages: 47-57
  • Peer Reviewed
• [Journal Article] Angiogenic Role of LYVE-1-positive Macrophages in Adipose Tissue. (2007)
  • Author(s): Cho CH, et. al.
  • Journal Title: Circ Res 100
  • Peer Reviewed
• [Journal Article] Angiopoietin-related growth factor (AGF) suppresses gluconeogenesis through the Akt/FoxO1-dependent pathway in hepatocytes. (2007)
  • Author(s): Kitazawa M, et. al.
  • Journal Title: J Pharmacol Exp Ther 323 Pages: 787-793
  • Peer Reviewed
• [Presentation] ANGPTLs : Potential New Targets for Metabolic Syndrome Therapy (2008)
  • Author(s): 尾池雄一
  • Organizer: 第16回日本血管生物医学会
  • Place of Presentation: 金沢
  • Year and Date: 2008-12-04
• [Presentation] 血管新生因子ANGPTLと肥満・メタボリックシンドローム (2008)
  • Author(s): 尾池雄一
  • Organizer: 第31回日本血栓止血学会・日本動脈硬化学会合同シンポジウム
  • Place of Presentation: 大阪
  • Year and Date: 2008-11-20
• [Presentation] 血管新生因子ANGPTLと肥満・メクボリックシンドローム (2008)
  • Author(s): 尾池雄一
  • Organizer: 第31回日本血栓止血学会・日本動脈硬化学会合同シンポジウム
  • Place of Presentation: 大阪
  • Year and Date: 2008-11-20
• [Presentation] アンジオポエチン様因子(ANGPTL)と血管・リンパ管 (2008)
  • Author(s): 尾池雄一
  • Organizer: 第29回日本炎症・再生医学会
  • Place of Presentation: 東京
  • Year and Date: 2008-07-09
• [Presentation] Angiopoietin-like proteins (Angptls) : potential new targets for metabolic syndrome therapy (2007)
  • Author(s): 尾池雄一
  • Organizer: ASIAN PACIFICO CONGRESS OF CARDIOLOGY
  • Place of Presentation: 台湾
  • Year and Date: 2007-12-12
• [Presentation] Angiopoietin-like proteins (Angptls): potential new targets for metabolic syndrome therapy (2007)
  • Author(s): 尾池 雄一
  • Organizer: ASIAN PACIFICO CONGRESS OF CARDIOLOGY
  • Place of Presentation: 台湾
  • Year and Date: 2007-12-12
• [Presentation] アンジオポエチンファミリーとリンパ管・血管ーリンパ管・血管標的抗がん療法を目指してー (2007)
  • Author(s): 尾池雄一
  • Organizer: 第1回日本血管生物医学会学術大会
  • Place of Presentation: 福岡
  • Year and Date: 2007-11-29
• [Presentation] アンジオポエチンファミリーとリンパ管・血管-リンパ管・血管標的抗がん療法を目指して (2007)
  • Author(s): 尾池 雄一
  • Organizer: 第15回日本血管生物医学会学術大会
  • Place of Presentation: 福岡
  • Year and Date: 2007-11-29
• [Presentation] Angiopoietin-like proteins(Angptls):potential new targets for metabolic syndrome therapy (2007)
  • Author(s): 尾池 雄一
  • Organizer: KSMBMB2007
  • Place of Presentation: 韓国
  • Year and Date: 2007-10-24
• [Presentation] Angiopoietin-like proteins (Angptls) : potential new targets for metabolic syndrome therapy (2007)
  • Author(s): 尾池雄一
  • Organizer: KSMBMB2007
  • Place of Presentation: 韓国
  • Year and Date: 2007-10-19
• [Presentation] ANGPTL2の機能解析 (2007)
  • Author(s): 尾池雄一
  • Organizer: 第28回日本肥満学会
  • Place of Presentation: 東京
  • Year and Date: 2007-10-19
• [Presentation] 肥満を標的としたメタボリックシンドロームの治療戦略 (2007)
  • Author(s): 尾池雄一
  • Organizer: 第28回日本肥満学会
  • Place of Presentation: 東京
  • Year and Date: 2007-10-19
• [Presentation] 肥満を標的としたメタボリックシンドロームの治療戦略 (2007)
  • Author(s): 尾池雄一
  • Organizer: 第44回日本臨床分子医学会学術集会
  • Place of Presentation: 和歌山
  • Year and Date: 2007-07-19