The development of the anti-angiogenic factor VEGF-A165b quantification methods for cardiovascular disease.

• Project/Area Number: 26860367
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Laboratory medicine
• Research Institution: Nagoya University
• Principal Investigator: KIKUCHI RYOSUKE 名古屋大学, 医学部附属病院, 臨床検査技師 (30721435)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: VEGF-A / 臨床検査医学 / VEGF-A165b / 血管新生 / 抗血管新生因子 / 微小血管障害 / マウス下肢虚血モデル / 代謝障害

Outline of Final Research Achievements

The VEGF-A165 (pro-angiogenic) and VEGF-A165b (anti-angiogenic), only the sequence of 6 amino acid residues of the C- terminal side is different. The current ELISA system of VEGF-A does not discriminate between different VEGF-A isoforms (pro- or anti-angiogenic forms). Here, we made the development of VEGF-A165b specific ELISA system, and the clarified the molecular mechanisms of VEGF-A165b.
Moreover, the urinary VEGF-A165b concentration was found to be useful for the development assessment of renal dysfunction.

Research Products

• [Journal Article] Secreted frizzled-related protein 5 diminishes cardiac inflammation and protects the heart from ischemia-reperfusion injury. (2016)
  • Author(s): Nakamura K, Sano S, Fuster JJ, Kikuchi R, Shimizu I, Ohshima K, Katanasaka Y, Ouchi N, Walsh K.
  • Journal Title: J Biol Chem Volume: 291 Issue: 6 Pages: 2566-2575
  • DOI: 10.1074/jbc.m115.693937
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] An antiangiogenic isoform of VEGF-A contributes to impaired vascularization in peripheral artery disease. (2014)
  • Author(s): Kikuchi R, Nakamura K, MacLauchlan S, Ngo DT, Shimizu I, Fuster JJ, Katanasaka Y, Yoshida S, Qiu Y, Yamaguchi TP, Matsushita T, Murohara T, Gokce N, Bates DO, Hamburg NM, Walsh K
  • Journal Title: Nat Med Volume: 20(12) Issue: 12 Pages: 1464-71
  • DOI: 10.1038/nm.3703
  • Peer Reviewed
• [Journal Article] Angiotensin II receptor blocker ameliorates stress-induced adipose tissue inflammation and insulin resistance. (2014)
  • Author(s): Hayashi M, Takeshita K, Uchida Y, Yamamoto K, Kikuchi R, Nakayama T, Nomura E, Cheng XW, Matsushita T, Nakamura S, Murohara T.
  • Journal Title: PLoS One Volume: 9 Issue: 12 Pages: e116163-e116163
  • DOI: 10.1371/journal.pone.0116163
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Anti-angiogenic actions of VEGF-A165b, a novel isoform of VEGF-A, in human obesity (2014)
  • Author(s): Doan TM, Farb M, Kikuchi R, Karki S, Tiwari S, Bigornia S, Bates DO, Hamburg NM, Vita JA, Hess DT, Walsh K, Gokce N
  • Journal Title: Circulation Volume: 130 Issue: 13 Pages: 1072-1080
  • DOI: 10.1161/circulationaha.113.008171
  • Peer Reviewed
• [Journal Article] Association of circulating C1q/TNF-related protein 1 levels with coronary artery disease in men. (2014)
  • Author(s): Yuasa D, Ohashi K, Shibata R, Takeshita K, Kikuchi R, Takahashi R, Kataoka Y, Miyabe M, Joki Y, Kambara T, Uemura Y, Matsuo K, Hayakawa S, Hiramatsu-Ito M, Ito M, Ikeda N, Murohara T, Ouchi N.
  • Journal Title: PLoS One Volume: 8 Issue: 6 Pages: e99846-e99846
  • DOI: 10.1371/journal.pone.0099846
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Vascular rarefaction mediates whitening of brown fat in obesity (2014)
  • Author(s): Shimizu I, Tamar A, Kikuchi R, Shimizu A, Papanicolaou K, MacLauchlan S, Maruyama S, Walsh K,
  • Journal Title: J. Clin. Invest Volume: 124(5) Issue: 5 Pages: 2099-2112
  • DOI: 10.1172/jci71643
  • Peer Reviewed
• [Presentation] Urinary VEGF-A165b and estimated glomerular filtration rate - Does urinary VEGF-A165b estimate kidney function ? - (2016)
  • Author(s): Ryosuke Kikuchi, Yasuda Yoshinori, Hiroyuki Matsumoto, Toyoaki Murohara, Tadashi Matsushita.
  • Organizer: The 32nd World congress of biomedical laboratory science
  • Place of Presentation: 神戸国際会議場(兵庫県神戸市)
  • Year and Date: 2016-08-30
  • Int'l Joint Research
• [Presentation] VEGF-A165bと血管病・肥満症との関連性から腎機能検査への応用 (2016)
  • Author(s): 菊地良介
  • Organizer: 腎・泌尿器検査研究会 第12回学術集会
  • Place of Presentation: 東京女子医科大学(東京都新宿区)
  • Year and Date: 2016-03-26
  • Invited
• [Presentation] 重症虚血肢へのヒト脂肪組織由来間葉系前駆細胞移植の治療効果判定指標としての臨床検査法探索研究. (2016)
  • Author(s): 菊地良介
  • Organizer: 第2回日本血管生物医学会若手研究会
  • Place of Presentation: 東北大学加齢医学研究所 スマートエージング国際共同研究センター (宮城県仙台市)
  • Year and Date: 2016-03-05
• [Presentation] VEGF-A抗血管新生アイソフォームを標的とした検査法開発に向けて －基礎研究成果から臨床検査への応用－ (2015)
  • Author(s): 菊地良介
  • Organizer: 第55回日本臨床化学年次学術集会 若手シンポジウム
  • Place of Presentation: 大阪大学コンベンションセンター(大阪府大阪市)
  • Year and Date: 2015-10-30
  • Invited
• [Presentation] 血管新生とVEGF-Aパラドックス - 抗血管新生因子VEGF-A165bの可能性 - (2015)
  • Author(s): 菊地良介
  • Organizer: 第1回Cardiac Research Meeting
  • Place of Presentation: 豊橋市民病院(愛知県豊橋市)
  • Year and Date: 2015-10-14
  • Invited
• [Presentation] Anti-angiogenic Actions of VEGF-A inhibitory isoform in Human Obesity (2015)
  • Author(s): Ryosuke Kikuchi, Hiroyuki Matsumoto, Tadashi Matsushita
  • Organizer: 第64回日本医学検査学会学術集会
  • Place of Presentation: 福岡国際会議場 (福岡県・ 博多市)
  • Year and Date: 2015-05-16 – 2015-05-17
• [Presentation] Anti-angiogenic Actions of VEGF-A inhibitory isoform in Human Obesity (2015)
  • Author(s): Ryosuke Kikuchi, Hiroyuki Matsumoto, Tadashi Matsushita
  • Organizer: 第64回日本医学検査学会学術集会
  • Place of Presentation: 福岡国際会議場 (福岡県博多市)
  • Year and Date: 2015-05-16
• [Presentation] Sfrp5/Wnt5aシグナリングによる抗血管新生因子VEGF-A165bを介した血管新生抑制について (2015)
  • Author(s): 菊地良介
  • Organizer: 第1回日本血管生物医学会若手研究会
  • Place of Presentation: 東京大学 (東京都・ 文京区)
  • Year and Date: 2015-02-06 – 2015-02-07
• [Presentation] The Sfrp5 / Wnt5a / VEGF-A165b axis as a new regulator of vascular response to tissue ischemia (2015)
  • Author(s): Ryosuke Kikuchi, Kenneth Walsh, Toyoaki Murohara
  • Organizer: 第3回IRG meeting
  • Place of Presentation: 品川プリンスホテル (東京都・ 港区)
  • Year and Date: 2015-01-16 – 2015-01-17
• [Presentation] VEGF-A165b, the potential as a novel biomarker of obesity-related disorders. (2014)
  • Author(s): Ryosuke Kikuchi, Kenneth Walsh, Hiroyuki Matsumoto, Tadashi Matsushita
  • Organizer: The 31th World congress of biomedical laboratory science (IFBLS)
  • Place of Presentation: 台北 (台湾)
  • Year and Date: 2014-10-03 – 2014-10-07
• [Presentation] Role of an anti-angiogenic isoform of VEGF-A, VEGF-A165b, in type 2 diabetes (2014)
  • Author(s): Ryosuke Kikuchi, Kenneth Walsh, Hiroyuki Matsumoto, Tadashi Matsushita
  • Organizer: 第63回日本医学検査学会学術集会
  • Place of Presentation: 新潟コンベンションセンター (新潟県・ 新潟市)
  • Year and Date: 2014-05-17 – 2014-05-18
• [Book] 細胞工学 1月号：抗血管新生因子としてのVEGF-A (2016)
  • Author(s): 松本健、依馬正次、樋田京子、間石奈湖、高倉伸幸、南敬、新藤隆行、伊東史子、佐藤靖史、菊地良介
  • Total Pages: 88
  • Publisher: 学研メディカル秀潤社
• [Book] 週刊 「医学のあゆみ」: 血管新生とVEGF-Aパラドックス - 抗血管新生因子VEGF-A165bの可能性- (2015)
  • Author(s): 中島淳、岡田克典、千田雅之、井上匡美、大谷真二、伊達洋至、白石武史、岩崎昭憲、鈴木秀海、吉野一郎、宮崎拓郎、永安武、安樂真樹、中島淳、岩月幸一、坪井直穀、菊地良介、唐文涛、津谷喜一郎、中澤港、安室芳樹、廣田耕志、武田俊一
  • Total Pages: 65
  • Publisher: 医歯薬出版株式会社
• [Book] 感染・炎症・免疫：VEGF-Aの相反する二面性 - VEGF-A血管新生抑制型アイソフォームとPAD - (2015)
  • Author(s): 藤永由佳子、安友康二、後藤義幸、鈴木忠樹、堀田博、鯉渕智彦、福永肇、舘田一博、住友秀次、森大輝、廣田圭司、菊地良介、木村博一、大久保裕、森川茂、駒瀬勝啓、中岡良和
  • Total Pages: 93
  • Publisher: 鳥居薬品株式会社
• [Book] 日本血栓止血学会誌 トピック：VEGF-A 抗血管新生アイソフォームと血管新生障害 (2015)
  • Author(s): 山本晃士、長尾毅彦、佐藤稔、中神啓徳、西條美佐、菅波孝祥、小川佳宏、内藤篤彦、野間玄督、木原康樹、東幸仁、宮田敏男、丹羽利充、菊地良介、辰巳公平 、一瀬白帝、柏木浩和、岡田清孝、加藤勝洋、左近賢人
  • Total Pages: 102
  • Publisher: 日本血栓止血学会
• [Remarks] 名古屋大学医学部附属病院 医療技術部 臨床検査部門
  • URL: http://www.med.nagoya-u.ac.jp/labmed/index.html
• [Patent(Industrial Property Rights)] 尿中VEGF-A165bを指標とした腎機能の検査方法及び検査装置、腎機能検査装置として機能させるためのプログラム及び記録媒体 (2015)
  • Inventor(s): 菊地良介、松下正、室原豊明
  • Industrial Property Rights Holder: 名古屋大学
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2015-110113
  • Filing Date: 2015-05-29