The role of VEGFR1 on angiogenesis in ischemic tissue

• Project/Area Number: 21791331
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Thoracic surgery
• Research Institution: Kitasato University
• Principal Investigator: AMANO Hideki Kitasato University, 医学部, 助教 (60296481)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2009: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 血管新生 / VEGFR1TK / 下肢虚血モデル / 骨髄由来

Research Abstract

Vascular endothelial growth factor (VEGF) is essential for developmental and pathological angiogenesis. Two VEGF receptors tyrosine kinase have been identified, VEGFR1 and VEGFR2. These two receptors are involved in angiogenesis but the molecular base of their actions is not well understood. Here we report that in murine ischemic hind limb model and tumor implanted model using deletion of domain of VEGFR1 decreased the recovery from ischemic condition. VEGFR1 TK-/- mice exhibited delayed blood flow recovery from ischemia and impaired angiogenesis compared to wild type mice. Furthemore, compared to wild type mice, plasma level of stem cell actor (SCF), stromal derived factor-1 (SDF-1) and pro-MMP-9 were decreased in VEGFR1TK-/-. Bone marrow derived CXCR4+VEGFR1+cells were significantly decreased in VEGFR1TK-/- mice compared to WT. Wild type mice transplanted VEGFR1 TK-/-bone marrow decreased the recovery from ischemic condition compared to wild type mice transplanted with wild type mice. These results suggested that the VEGFR1 TK signaling modulates the mobilization of bone marrow cells to ischemic muscle

Research Products

• [Journal Article] Calcitonin gene-related peptide facilitates revascularization during hindlimb ischemia in mice. (2011)
  • Author(s): Mishima T, Ito Y, Hosono K, Tamura Y, Uchida Y, Hirata M, Suzsuki T, Amano H, Kato S, Kurihara Y, Kurihara H, Hayashi I, Watanabe M, Majima M.
  • Journal Title: Am J Physiol Heart Circ Physiol. Volume: 2 Pages: 431-439
  • Peer Reviewed
• [Journal Article] Combined Effect of Anti-Angiogentic Agents, Angiotensin Type 1 Receptor Antagonists and Radiation Therapy. (2010)
  • Author(s): Amano H, Ohnuma Y, Niibe Y, Hayakawa K, Satoh Y, Majima M
  • Journal Title: Current Signal Transduction TherapCurrent Therapy 5(3) Pages: 206-211
  • Peer Reviewed
• [Journal Article] Effect of erythropoietin on angiogenesis with increased adhesion of platelets to the microvessels in the hind-limb ischemia (2010)
  • Author(s): Kato S, Amano H, Ito Y, Eshima K, Aoyama N, Tamaki H, Sakagami H, Satoh Y, Izumi T, Majima M
  • Journal Title: J.Pharmacol Sci 112(2) Pages: 167-175
  • Peer Reviewed
• [Journal Article] Host prostaglandin EP3 receptor signaling relevant to tumor-associated lymphangiogensis (2010)
  • Author(s): Kubo H, Hosono K, Suzuki T, Ogawa Y, Kato H, Kamata H, Ito Y, Amano H, Kato T, Sakagami H, Hayashi I, Sugimoto Y, Narumiya S, Watanabe M, Majima M
  • Journal Title: Biomed. Pharmacother 64(2) Pages: 101-106
  • Peer Reviewed
• [Journal Article] Recruited bone marrow cells expressing the EP3 prostaglandin E receptor subtype enhance angiogenesis during chronic inflammation. (2010)
  • Author(s): Ueno T, Suzuki T, Oikawa A, Hosono K, Kosaka Y, Amano H, Kitasato H, Toda M, Hayashi I, Kato T, Ito Y, Sugimoto Y, Narumiya S, Okamoto H, Majima M
  • Journal Title: Biomed. Pharmacother 64(2) Pages: 93-100
  • Peer Reviewed
• [Journal Article] Combined Effect of Anti-Angiogentic Agents, Angiotensin Type 1 Receptor Antagonists and Radiation Therapy. (2010)
  • Author(s): Amano Hideki
  • Journal Title: Current Signal Transduction Therapy Volume: 5 Pages: 206-211
  • Peer Reviewed
• [Journal Article] Thymic large cell neuroendocrine carcinoma : report of a resected case-a case report (2010)
  • Author(s): Ogawa F, Iyoda A, Amano H, Nezu K, Jiang SX, Okayasu I, Satoh Y.
  • Journal Title: J Cardiothorac Surg Volume: 5 Pages: 115-115
  • Peer Reviewed
• [Journal Article] Effect of Erythropoietin on Angiogenesis With the Increased Adhesion of Platelets to the Microvessels in the Hind-Limb Ischemia Model in Mice (2010)
  • Author(s): Kato S, Amano H, lto Y, Eshima K, Aoyama N, Tamaki H, Sakagami H, Satoh Y, Izumi T, Majima M
  • Journal Title: J Pharmacol Sci. 112(2) Pages: 167-75
  • NAID: 10029888784
  • Peer Reviewed
• [Journal Article] Host prostaglandin EP3 receptor signaling relevant totumor associated lymphangiogenesis. (2010)
  • Author(s): Kubo H, Hosono K, Suzuki T, Ogawa Y, Kato H, Kamata H, lto Y, Amano H, Kato T, Sakagami H, Hayashil, Sugimoto Y, Narumiya S, Watanabe M, Majima M.
  • Journal Title: Biomed Pharmacother. 64(2) Pages: 101-6
  • Peer Reviewed
• [Journal Article] Roles of a Prostaglandin E type Receptor, EP3, in upregulation of matrix metalloproteinase-9 and vascular endothelial growth factor during enhancement of tumor metastasis (2009)
  • Author(s): Amano H, Ito Y, Suzuki T, Kato S, Ogawa F, Murata T, Sugimoto Y, Senior R, Kitasato H, Hayashi I, Satoh Y, Narumiya S, Majima M
  • Journal Title: Cancer Sci 100(12) Pages: 2318-24
  • NAID: 10027198074
  • Peer Reviewed
• [Journal Article] Bone marrow-derived EP3-expressing stromal cells enhance tumor-associated angiogenesis and tumor growth (2009)
  • Author(s): Ogawa Y, Suzuki T, Oikawa A, Hosono K, Kubo H, Amano H, Ito Y, Kitasato H, Hayashil, Kato T, Sugimoto Y, Narumiya S, Watanabe M, Majima M.
  • Journal Title: BBRC 382(4) Pages: 720-5
  • Peer Reviewed
• [Presentation] Angiogenesis enhanced by TP signal-mediated platelet adhesion to neovasculized endothelial cells with CXCR4+VEGFR1+ cells mobilization during hindlimb ischemia. (2010)
  • Author(s): Amano, H., Kato, S., Ito, Y., Satoh, Y., Majima, M.
  • Organizer: 9^<th> World Congress for Microcirculation(P53)
  • Place of Presentation: Paris
  • Year and Date: 2010-09-28
• [Presentation] Angiogenesis enhanced by TP signal-mediated platelet adhesion to neovasculized endothelial cells with CXCR4+VEGFR1+ cells mobilization during hindlimb ischemia. (2010)
  • Author(s): 天野英樹
  • Organizer: 第9回国際微小循環学会
  • Place of Presentation: パリ(フランス)(シンポジスト)
  • Year and Date: 2010-09-28
• [Presentation] Role of Angiotensin type 1a receptor signaling on tumor metastasis formation (2010)
  • Author(s): Amano, H., Fukui, T.Matsui, Y., Ito, Y., Kato, S., Ogawa, F., Kuroudu, N., Nezu, K., Iyoda, A., Satoh, Y., Majima, M.
  • Organizer: 69^<th> Annual Meeting of the Japanese Cancer Association(P135)
  • Place of Presentation: Osaka
  • Year and Date: 2010-09-23
• [Presentation] 腫瘍肺転移形成におけるAT1aシグナリングのメカニズムの解析 (2010)
  • Author(s): 天野英樹、伊藤義也、松井啓夫、小川史洋、原英則、根津賢司、伊豫田明、佐藤之俊, 馬嶋正隆
  • Organizer: 炎症再生学会(P244)
  • Place of Presentation: 東京
  • Year and Date: 2010-08-06
• [Presentation] Angiotensin type 1a receptor signaling-dependent induction of platelet production is relevant to tumor metastasis (2009)
  • Author(s): Amano H, Ito Y, Suzuki T, Kato S, Ogawa F, Murata T, Sugimoto Y, Senior R, Kitasato H, Hayashi I, Satoh Y. Narumiva S. Maiima M
  • Organizer: 第68回日本癌学会
  • Place of Presentation: パシフィコ横浜(神奈川)
• [Presentation] Tumor growth and metastasis are enhanced with Thromboxane A2-TP receptor signaiing through platelet activity and production (2009)
  • Author(s): Amano H, Ito Y, Suzuki T, Kato S, Ogawa F, Murata T, Sugimoto Y, Senior R, Kitasato H, Hayashi I, Satoh Y. Narumiva S. Majima M
  • Organizer: 第9回国際炎症学会
  • Place of Presentation: 京王プラザホテル(東京)
• [Presentation] Lung metastasis and growth of the tumors are enhanced with Thromboxane A2-TP receptor through platelet activity and production (2009)
  • Author(s): Amano H, Ito Y, Suzuki T, Kato S, Ogawa F, Murata T, Sugimoto Y, Senior R, Kitasato H, Hayashi I, Satoh Y, Narumiva S. Majima M
  • Organizer: 第13回世界肺癌学会
  • Place of Presentation: サンフランシスコ(米国)
• [Remarks] ホームページ等
• [Remarks] 研究論文の掲載について北里大学薬理学のホームページに記載した