Analysis of ARIA that is a novel gene regulating endothelial apoptosis in the regulation of neovessel formation

• Project/Area Number: 20590885
• 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: Kyoto Prefectural University of Medicine
• Principal Investigator: IKEDA Koji Kyoto Prefectural University of Medicine, 医学研究科, 助教 (90423871)
• Co-Investigator(Renkei-kenkyūsha): MATSUBARA Hiroaki 京都府立医科大学, 医学研究科, 教授 (10239072)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2010: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2008: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 分子血管病態学 / 血管新生 / 血管内皮細胞 / アポトーシス / PI3K / Akt

Research Abstract

We have generated ARIA (former BLADE) knockout mice, and analyzed the ARIA function in the regulation of neovessel formation. By using the hind-limb ischemia model, we revealed that genetic deletion of ARIA substantiallyenhanced the ischemia-induced neovascularization. Moreover, we found that ARIA is highly expressed in endothelial progenitor cells as well, and regulates their angiogenic functions by modulating the PI3K/Akt pathway.

Research Products

• [Journal Article] Apoptosis regulator through modulating IAP expression (ARIA) regulates the PI3K/Akt pathway in endothelial and endothelial progenitor cells. (2011)
  • Author(s): Koide M, Ikeda K (corresponding author), Akakabe Y, Kitamura Y, Ueyama T, Matoba S, Yamada H, Okigaki M, Matsubara H.
  • Journal Title: Proc Natl Acad Sci USA in press
• [Journal Article] Endothelial FGF receptor signaling accelerates atherosclerosis. (2011)
  • Author(s): Che J, Okigaki M, Takahashi T, Katsume A, Adachi Y, Yamaguchi S, Matsunaga S, Takeda M, Matsui A, Kishita E, Ikeda K, Yamada H, Matsubara H.
  • Journal Title: Am J Physiol Heart Circ Physiol. 300(1)
• [Journal Article] p53 and TIGAR regulate cardiac myocyte energy homeostasis under hypoxic condition. (2010)
  • Author(s): Kimata M, Matoba S, Iwai-Kanai E, Nakamura H, Hoshino A, Nakaoka M, Katamura M, Okawa Y, Mita Y, Okigaki M, Ikeda K, Tatsumi T, Matsubara H.
  • Journal Title: Am J Physiol Heart Circ Physiol. 299(6)
• [Journal Article] Paracrine osteogenic signals via bone morphogenetic protein-2 accelerate the atherosclerotic intimal calcification in vivo. (2010)
  • Author(s): Nakagawa Y, Ikeda K (corresponding author), Akakabe Y, Koide M, Uraoka M, Yutaka KT, Kurimoto-Nakano R, Takahashi T, Matoba S, Yamada H, Okigaki M, Matsubara H.
  • Journal Title: Arterioscler Thromb Vasc Biol. 30(10) Pages: 1908-1915
• [Journal Article] Pathophysiology of vascular calcification : pivotal role of cellular senescence in vascular smooth muscle cells. (2010)
  • Author(s): Burton DG, Matsubara H, Ikeda K (last author).
  • Journal Title: Exp Gerontol. 45(11) Pages: 819-824
• [Journal Article] Bone marrow AT1 augments neointimal formation by promoting mobilization of smooth muscle progenitors via platelet-derived SDF-1alpha. (2010)
  • Author(s): Yokoi H, Yamada H, Tsubakimoto Y, Takata H, Kawahito H, Kishida S, Kato T, Matsui A, Hirai H, Ashihara E, Maekawa T, Iwai M, Horiuchi M, Ikeda K, Takahashi T, Okigaki M, Matsubara H.
  • Journal Title: Arterioscler Thromb Vasc Biol. 30(1) Pages: 60-67
• [Journal Article] Paracrine osteogenic signals via bone morphogenetic protein-2 accelerate the atherosclerotic intimal calcification in vivo. (2010)
  • Author(s): Nakagawa Y, Ikeda K, Akakabe Y, Koide M, Uraoka M, Yutaka KT, Kurimoto-Nakano R, Takahashi T, Matoba S, Yamada H, Okigaki M, Matsubara H.
  • Journal Title: Arterioscler Thromb Vasc Biol. Volume: 30 Pages: 1908-1915
  • Peer Reviewed
• [Journal Article] Pathophysiology of vascular calcification : pivotal role of cellular senescence in vascular smooth muscle cells. (2010)
  • Author(s): Burton DG, Matsubara H, Ikeda K.
  • Journal Title: Exp Gerontol. Volume: 45 Pages: 819-824
  • Peer Reviewed
• [Journal Article] Identification of ARIA regulating endothelial apoptosis and angiogenesis by modulating proteasomal degradation of cIAP-1 and cIAP-2 (2009)
  • Author(s): Ikeda K, Nakano R, Uraoka M, Nakagawa Y, Koide M, Katsume A, Minamino K, Yamada E, Yamada H, Quertermous T, Matsubara H
  • Journal Title: Proc Natl Acad Sci USA 106 Pages: 82278232-82278232
  • Peer Reviewed
• [Journal Article] Replicative senescent vascular smooth muscle cells enhances the calcification through initiating the osteoblastic transistion (2009)
  • Author(s): Nakano-Kurimoto R, Ikeda K, Uraoka M, Nakagawa Y, Yutaka K, Koide M, Takahashi T, Matoba S, Yamada H, Okigaki M, Matsubara H
  • Journal Title: Am J Physiol Heart Circ Physiol 297
  • Peer Reviewed
• [Journal Article] Prorenin induces ERK activation in endothelial cells to enhance neovascularization independently of the renin-angiotensin system (2009)
  • Author(s): Uraoka M, Ikeda K, Nakagawa Y, Koide M, Akakabe Y, Nakano-Kurimoto R, Takahashi T, Matoba S, Yamada H, Okigaki M, Matsubara H
  • Journal Title: Biochem Biophys Res Commun. 390 Pages: 12021207-12021207
  • Peer Reviewed
• [Presentation] ARIA regulates ischemia-induced angiogenesis and vasculogenesis through modulating the PI3K/Akt/eNOS signaling pathway. (2010)
  • Author(s): Koide M, Ikeda K, Kitamura Y, Akakabe Y, Nakagawa Y, Matsubara H.
  • Organizer: AHA scientific sessions, Circulation 122(23) : A-14736
• [Presentation] Identification of ARIA as a novel factor regulating endothelial cell apoptosis and angiogenesis in vivo. (2010)
  • Author(s): Koide M, Ikeda K, Nakagawa Y, Akakabe Y, Kurimoto R, Matsubara H.
  • Organizer: 第74回日本循環器学会学術総会
  • Place of Presentation: 京都
• [Presentation] Identification of ARIA as a novel factor regulating endothelial apoptosis and angiogenesis in vivo. (2010)
  • Author(s): Koide M, Ikeda K, Akakabe Y, Uraoka M, Nakagawa Y, Kurimoto R, Matsubara H.
  • Organizer: 心血管内分泌学会
  • Place of Presentation: 奈良
• [Presentation] Identification of ARIA as a novel factor regulating endothelial cell apoptosis and angiogenesis in vivo. (2009)
  • Author(s): Masahiro Koide, Koji Ikeda, Maki Uraoka, Yusuke Nakagawa, Yoshiki Akakabe, Ritsuko Kurimoto, Hiroaki Matsubara.
  • Organizer: American Heart Association(米国心臓病学術会議)
  • Place of Presentation: Orlando, USA
• [Presentation] Molecular identification and characterization of a novel gene thatregulates endothetial cell apoptosis and angiogenesis (2008)
  • Author(s): Koji Ikeda
  • Organizer: アメリカ心臓病学会
  • Place of Presentation: 米国ニューオーリンズ
• [Book] 血管新生療法(循環器疾患-疾患モデルの作成と利用)第2章9節 (2010)
  • Author(s): 池田宏二, 他
  • Publisher: 株式会社エル・アイ・シー
• [Book] 循環器疾患-疾患モデルの作成と利用第2章 第9節 血管新生療法 (2010)
  • Author(s): 池田宏二
  • Publisher: 株式会社 エル・アイ・シー
• [Remarks] ホームページ等
  • URL: http://www.f.kpu-m.ac.jp/k/med2/index.html
• [Remarks]
  • URL: http://www.f.kpu-m.ac.jp/k/med2/
• [Remarks]
  • URL: http://www.f.kup-m.ac.jp/k/med2/
• [Patent(Industrial Property Rights)] 肥満・インスリン感受性を制御する遺伝子およびそのノックアウト動物および本意電子の機能調節を介した肥満及び/又はメタボリック症候群の予防及び/又は治療薬のスクリーニング (2011)
  • Inventor(s): 池田宏二、松原弘明、赤壁佳樹
  • Industrial Property Rights Holder: 池田宏二、松原弘明、赤壁佳樹
  • Industrial Property Number: 2011-009375
  • Filing Date: 2011-01-20