Development of angiogenetic and regenerative therapy with regulation of Notch signaling

• Project/Area Number: 19590859
• 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: Nagoya University
• Principal Investigator: TAKESHITA Kyosuke Nagoya University, 大学院・医学系研究科, 特任助教 (70444403)
• Co-Investigator(Kenkyū-buntansha): NUMAGUCHI Yasushi 名古屋大学, 医学部, 寄附講座准教授 (90378224) ; SHINTANI Satoshi 名古屋大学, 大学院・医学系研究科, 講師 (20309777) ; SHIBATA Rei 名古屋大学, 大学院・医学系研究科, 特任助教 (70343689) ; MUROHARA Toyoaki 名古屋大学, 大学院・医学系研究科, 教授 (90299503)
• 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: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2007: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 血管新生 / 血管内皮細胞 / Notchシグナル

Research Abstract

血管新生は既存の血管から新たな血管枝が分岐して血管網を構築する生理的現象であり、その制御は、虚血をきたした組織の血流の改善、あるいはがん細胞増殖の抑制のために重要な治療ポイントである。本研究では、受精卵から成体になる過程で重要な役割を果たすことで知られるNotchシグナルが、成体の虚血組織の血管新生においても重要であることを、細胞内シグナル解析および遺伝子改変マウスを用いて明らかにした。

Research Products

• [Journal Article] Caloric restriction stimulates revascularization in response to ischemia via adiponectin-mediated activation of endothelial nitric-oxide synthase (2009)
  • Author(s): Kondo M, Shibata R, Miura R, Shimano M, Kondo K, Li P, Ohashi T, Kihara S, Maeda N, Walsh K, Ouchi N, Murohara T
  • Journal Title: J Biol Chem. 284(3) Pages: 1718-24
  • Peer Reviewed
• [Journal Article] Implantation of adipose-derived regenerative cells enhances ischemia-induced angiogenesis (2009)
  • Author(s): Kondo K, Shintani S, Shibata R, Murakami H, Murakami R, Imaizumi M, Kitagawa Y, Murohara T
  • Journal Title: Arterioscler Thromb Vasc Biol 29(1) Pages: 61-6
  • Peer Reviewed
• [Journal Article] Pioglitazone attenuates cardiac hypertrophy in rats with salt-sensitive hypertension : role of activation of AMP-activated protein kinase and inhibition of Akt (2008)
  • Author(s): Kato MF, Shibata R, Obata K, Miyachi M, Yazawa H, Tsuboi K, Yamada T, Nishizawa T, Noda A, Cheng XW, Murate T, Koike Y, Murohara T, Yokota M, Nagata K
  • Journal Title: J Hypertens 26(8) Pages: 1669-76
  • Peer Reviewed
• [Journal Article] Circulating adiponectin levels in patients with atrial fibrillation (2008)
  • Author(s): Shimano M, Shibata R, Tsuji Y, Kamiya H, Uchikawa T, Harata S, Muto M, Ouchi N, Inden Y, Murohara T
  • Journal Title: Circ J. 72(7) Pages: 1120-4
  • NAID: 110006792065
  • Peer Reviewed
• [Journal Article] Circulating homocysteine levels in patients with radiofrequency catheter ablation for atrial fibrillation (2008)
  • Author(s): Shimano M, Inden Y, Tsuji Y, Kamiya H, Uchikawa T, Shibata R, Murohara T
  • Journal Title: Europace 10(8) Pages: 961-6
  • Peer Reviewed
• [Journal Article] Usefulness of adiponectin to predict myocardial salvage following successful reperfusion in patients with acute myocardial infarction (2008)
  • Author(s): Shibata R, Numaguchi Y, Matsushita K, Sone T, Kubota R, Ohashi T, Ishii M, Kihara S, Walsh K, Ouchi N, Murohara T
  • Journal Title: Am J Cardiol 101(12) Pages: 1712-5
  • Peer Reviewed
• [Journal Article] Adiponectin promotes endothelial progenitor cell number and function (2008)
  • Author(s): Shibata R, Skurk C, Ouchi N, Galasso G, Kondo K, Ohashi T, Shimano M, Kihara S, Murohara T, Walsh K
  • Journal Title: FEBS Lett. 582(11) Pages: 1607-12
  • 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, Yano M, Kadomatsu T, Yasunaga K, Shibata R, Murohara T, Akaike T, Tanihara H, Suda T, Oike Y
  • Journal Title: Arterioscler Thromb Vasc Biol 28(5) Pages: 827-34
  • Peer Reviewed
• [Journal Article] 加齢と血管新生能 (2008)
  • Author(s): 竹下享典
  • Journal Title: 血管医学 9(1) Pages: 57-63
• [Journal Article] 加齢と血管新生能 (2008)
  • Author(s): 竹下享典
  • Journal Title: 血管医学 9 Pages: 57-63
• [Journal Article] Pitavastatin attenuates the upregulation of tissue factor in restraint-stressed mice (2007)
  • Author(s): Yamamoto K, Kojima T, Takeshita K, Matsushita T, Takamatsu J
  • Journal Title: Thromb Res 120(1) Pages: 143-4
  • Peer Reviewed
• [Journal Article] Critical role of Endothelial notch1 Signaling in Postnatal Angiogenesis (2007)
  • Author(s): Takeshita K, Satoh M, Ii M, Silver M, Limbourg FP, Mukai Y, Rikitake Y, Radtke F, Greidly T, Losordo DW, Liao JK
  • Journal Title: Circ Res 100(1) Pages: 70-78
  • Peer Reviewed
• [Journal Article] Inhibition of Apoptosis-regulated Signaling Kinase-1 and Prevention of Congestive Heart Failure by Estrogen (2007)
  • Author(s): Satoh M, Matter CM, Ogita H, Takeshita K, Wang CY, Dorn GW 2^<nd>, Liao JK
  • Journal Title: Circulation 115(25) Pages: 3197-204
  • Peer Reviewed
• [Journal Article] 心筋の線維化とPlasminogen activator inhibitor-1 (2007)
  • Author(s): 竹下享典
  • Journal Title: 日本血栓止血学会誌18/1 66
  • NAID: 10026114371
• [Journal Article] Pitavastatin attenuates the upregulation of tissue factor in restraint-stressed mice (2007)
  • Author(s): Yamamoto K, Takeshita K
  • Journal Title: Thrombosis Research 120 Pages: 143-4
  • Peer Reviewed
• [Journal Article] Critical role of Endothelial notchl Signaling in Postnatal Angiogenesis (2007)
  • Author(s): Takeshita K
  • Journal Title: Circulation Research 100 Pages: 70-78
  • Peer Reviewed
• [Journal Article] 心筋の線維化とPlasminogen activator inhibitor-1 (2007)
  • Author(s): 竹下享典
  • Journal Title: 日本血栓止血学会誌 66 Pages: 66-70
  • NAID: 10026114371
• [Presentation] 動脈硬化予防の新しいアプローチ-基礎研究から新薬開発の可能性- (2008)
  • Author(s): Takeshita K, Kikuchi R, Aoyama T, Murohara T
  • Organizer: 第17回日本心血管インターベンション学会ファイアサイドシンポジウム1「虚血性心疾患の再発予防治療のup to date」
  • Place of Presentation: 名古屋
  • Year and Date: 2008-07-03
• [Presentation] Pitavastatin Augments Angiogenetic Activity in Human Endothelial Cells via Notch Signal Activation (2008)
  • Author(s): Kikuchi R, Takeshita K, Aoyama T, Murohara T
  • Organizer: The 81th American Heart Association conference
  • Place of Presentation: New Orleans, Louisiana, USA
• [Presentation] Gamma Secretase Inhibitor Reduces diet-induced Atherosclerosis in Mice by Inhibiting the Notch signaling pathway in inflammatory cells (2008)
  • Author(s): Aoyama T, Takeshita K, Liao JK, Murohara T
  • Organizer: Annual Meeting of Japan regeneration Society
  • Place of Presentation: Nagoya, Japan
• [Presentation] Pitavastatin Augments Angiogenetic Activity in Human Endothelial Cells via Notch Signal Activation (2008)
  • Author(s): Takeshita K,Aoyama T, Murohara T
  • Organizer: Annual Meeting of Japan Circulation Society
  • Place of Presentation: Fukuoka, Japan
• [Presentation] Notch Signal Is Involved in Intimal thickening and Macrophage Accumulation. Young Investigator Awards Competition Finalist (2008)
  • Author(s): Takeshita K,Aoyama T, Murohara T
  • Organizer: Annual Meeting of Japan Circulation Society
  • Place of Presentation: Fukuoka, Japan
• [Presentation] Critical Role of Vascular Smooth Muscle Notch1 in Mediating Neointima Formation (2007)
  • Author(s): Takeshita K
  • Organizer: The 8^<th>US-JAPAN-ASIA Dialogue on Cardiovascular Diseases
  • Place of Presentation: Grand Rounds with Brigham & Women's Hospital Tokyo, Japan
  • Year and Date: 2007-08-25
• [Presentation] Silent brain infarction predicts cardiovascular events and mortality in long-term hemodialysis patients (2007)
  • Author(s): Aoyama T, Ishii H, Takeshita K, Matsubara T, Murohara T
  • Organizer: The 80^<th> American Heart Association conference
  • Place of Presentation: New Orlins, Frolida, USA
• [Presentation] Gamma Secretase Inhibitor Reduces diet-induced Atherosclerosis in Mice by Inhibiting the Notch signaling pathway in inflammatory cells (2007)
  • Author(s): Aoyama T, Takeshita K, Liao JK, Murohara T
  • Organizer: The 80th American Heart Association conference
  • Place of Presentation: Orlando, Florida, USA