Development of the molecular imaging and the therapy of the unstable plaque targeting activated macrophages

2013 Fiscal Year Final Research Report

• Project/Area Number: 23591105
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Kagoshima University
• Principal Investigator: MIYATA MASAAKI 鹿児島大学, 医歯(薬)学総合研究科, 准教授 (00347113)
• Co-Investigator(Kenkyū-buntansha): MATSUYAMA Takami 鹿児島大学, 医歯学総合研究科, 教授 (30145479)
• Co-Investigator(Renkei-kenkyūsha): FURUSHO Yuko 鹿児島大学, 医歯学総合研究科, 助教 (00632514)
• Project Period (FY): 2011 – 2013
• Keywords: 動脈硬化 / 葉酸レセプターβ / マクロファージ

Research Abstract

The folic acid receptor beta (FR-beta) attracts attention as a marker of activated macrophages. We found that the activated macrophage which expressed FR-beta was present in the arteriosclerosis lesion of the arteriosclerosis model mouse. We administrated the recombinant immunotoxin which coupled Pseudomonas aeruginosa toxin to anti-FR-beta monoclonal antibody into the arteriosclerosis model mice, selectively killed the activated macrophages, and demonstrated that it reduced arteriosclerotic lesion.
In addition, we established a sandwich ELISA assay using anti-FR-beta monoclonal antibody and measured the soluble FR-beta concentration of human serum. The patients with aortic aneurysms showed a higher serum FR-beta level compared with the normal control. The measurement of the soluble FR-beta concentration is suggested to be useful for the diagnosis of atherosclerosis.

Research Products

• [Journal Article] Novel therapy for atherosclerosis using recombinant immunotoxin against folate receptorβ-expressing macrophages (2012)
  • Author(s): Furusho Y, Miyata M, Matsuyama T, Nagai T, Li H, Akasaki Y, Hamada N, Miyauchi T, Ikeda Y, Shirasawa T, Ide K, Tei C
  • Journal Title: J Am Heart Assoc Volume: 1 Pages: e003079
  • DOI: 10.1161/JAHA.112.003079
  • Peer Reviewed
• [Presentation] 高血圧と動脈硬化:その接点を探り、治療する (2012)
  • Author(s): 宮田昌明
  • Organizer: 第60回日本心臓病学会学術集会
  • Place of Presentation: 金沢
  • Year and Date: 20120900
• [Presentation] Topic 10「動脈硬化治療の最前線」Novel therapy for atherosclerosis targeting folate receptorβ-expressing activated macrophages (2012)
  • Author(s): Miyata M, Furusho Y, Tei C
  • Organizer: 第76回日本循環器学会学術集会
  • Place of Presentation: 福岡
  • Year and Date: 20120300
• [Presentation] New therapy for atherosclerosis targeting FRβ-expressing macrophages (2011)
  • Author(s): Furusho Y, Miyata M, Akasaki Y, Hamada N, Miyauchi T, Ikeda Y, Hamasaki S, Tei C
  • Organizer: Europian Society of Cardiology Congress 2011
  • Place of Presentation: Paris
  • Year and Date: 20110800
• [Remarks] 鹿児島大学産学官連携推進センター、研究シーズ集活性化マクロファージを標的とした動脈硬化の新規診断・治療法の開発【動脈硬化】
  • URL: http://www.rdc.kagoshima-u.ac.jp/rdc/search/upload/miyata-med.pdf
• [Remarks] 鹿児島大学研究者総覧、宮田昌明
  • URL: http://kuris.cc.kagoshima-u.ac.jp/407594.html
• [Remarks] 鹿児島大学大学院医歯学総合研究科心臓血管・高血圧内科学ホームページ
  • URL: http://www.kufm.kagoshima-u.ac.jp/~intmed1/
• [Patent(Industrial Property Rights)] 動脈硬化又は動脈硬化性疾患の治療剤、及び動脈硬化又は動脈硬化性疾患の診断薬 (2011)
  • Inventor(s): 宮田昌明、古庄優子、鄭忠和、永井拓、松山隆美
  • Industrial Property Rights Holder: 宮田昌明、古庄優子、鄭忠和、永井拓、松山隆美、鹿児島大学
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2011-153862
  • Filing Date: 2011-07-12
• [Patent(Industrial Property Rights)] 動脈硬化又は動脈硬化性疾患の治療剤、及び動脈硬化又は動脈硬化性疾患の診断薬 (2011)
  • Inventor(s): 宮田昌明、古庄優子、鄭忠和、永井拓、松山隆美
  • Industrial Property Rights Holder: 宮田昌明、古庄優子、鄭忠和、永井拓、松山隆美、鹿児島大学
  • Industrial Property Rights Type: 特許公開
  • Industrial Property Number: WO2012/063955
  • Filing Date: 2011-11-08
  • Overseas