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Development of new therapies and significance of adrenomedullin and mast cells in the abdominal aortic aneurysm.

Research Project

Project/Area Number 22390161
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionUniversity of Miyazaki

Principal Investigator

KITAMURA Kazuo  宮崎大学, 医学部, 教授 (50204912)

Co-Investigator(Kenkyū-buntansha) TSURUDA Toshihiro  宮崎大学, 医学系研究科, 講師 (10389570)
KATO Johji  宮崎大学, フロンティア科学実験総合センター, 教授 (20274780)
Project Period (FY) 2010-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2013: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2012: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2011: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2010: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Keywordsアドレノメデュリン / 腹部大動脈瘤 / マスト細胞 / 血管作動性ペプチド / 炎症性サイトカイン / 血管外膜 / 老化 / 炎症 / 外膜 / マクロファージ / トラニラスト / サイトカイン / コラゲナーゼ
Research Abstract

Abdominal aortic aneurysm (AAA) develops based on advanced atherosclerosis; however, the underlying pathogenesis remains unknown. Adrenomedullin (AM) is widely expressed in various organs and tissues, and has anti-inflammatory, anti-oxidant and angiogenic activity. We have reported that AM is produced in mast cells of human AAA and that AM exhibited the anti-fibrotic activity on fibroblasts. We investigated the role of AM in the development of AAA in 12 weeks-old male apoE-/- mice bred with AM heterozygous, or its role when recombinant human (rh)AM was administrated to the apoE-/- male mice, which was infused with 1000ng/kg/min of angiotensin II for 28 days. Mortality tended to be higher in rhAM at 3000ng/kg/hr. Both the incidence and the size of AAA were not significant between the groups. Because of dual nature of AM action on progression or protection of AAA, we may not have observed the biological actions of AM in the development of AAA.

Report

(5 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (36 results)

All 2014 2013 2012 2011 2010

All Journal Article (10 results) (of which Peer Reviewed: 10 results) Presentation (16 results) Book (7 results) Patent(Industrial Property Rights) (3 results)

  • [Journal Article] Adrenomedullin does not contribute toward the development of abdominal aortic aneurysm in mice2014

    • Author(s)
      Sakamoto S, Tsuruda T, Hatakeyama K, Shimosawa T, Asada Y, Kitamura K
    • Journal Title

      Health

      Volume: 6(10) Pages: 1077-1084

    • Related Report
      2013 Annual Research Report 2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition of development of abdominal aortic aneurysm by glycolysis restriction2012

    • Author(s)
      Tsuruda T, Hatakeyama K, Nagamachi S, Sekita Y, Sakamoto S, Endo GJ, Nishimura M, Matsuyama M, Yoshimura K, Sato Y, Onitsuka T, Imamura T, Asada Y, Kitamura K
    • Journal Title

      Arterioscler Thromb Vasc Biol

      Volume: 32 Pages: 1410-1417

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Inhibition of development of abdominal aortic aneurysm by glycolysis restriction.2012

    • Author(s)
      Tsuruda T, Hatakeyama K, Nagamachi S, Sekita Y, Sakamoto S, Endo GJ, Nishimura M, Matsuyama M, Yoshimura K, Sato Y, Onitsuka T, Imamura T, Asada Y, Kitamura K.
    • Journal Title

      Arterioscler Thromb Vasc Biol

      Volume: 32 Issue: 6 Pages: 1410-1417

    • DOI

      10.1161/atvbaha.111.237065

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Adrenomedullin : Roles for structure and function in cardiac or vascular tissues2011

    • Author(s)
      Tsuruda T, Kitamura K
    • Journal Title

      Current Hypertension Reviews

      Volume: 7 Pages: 268-272

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Function of the cytoplasmic tail of human calcitonin receptor-like receptor in complex with receptor activity-modifying protein 22010

    • Author(s)
      Kuwasako K, Kitamura K, Nagata S, Hikosaka T, Kato J
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 392 Pages: 380-385

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Plasma and tissue levels of proangiotensin-12 and components of the renin-angiotensin system (RAS) following low- or high-salt feeding in rats2010

    • Author(s)
      Nagata S, Kato J, Kuwasako K, Kitamura K
    • Journal Title

      Peptides

      Volume: 31 Pages: 889-892

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Stromal cell biology : a way to understand the evolution of cardiovascular diseases2010

    • Author(s)
      Tsuruda T, Imamura T, Hatakeyama K, Asada Y, Kitamura K
    • Journal Title

      Circ J

      Volume: 74 Pages: 1042-1050

    • NAID

      10026474117

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Function of the cytoplasmic tail of human calcitonin receptor-like receptor incomplex with receptor activity-modifying protein 2.2010

    • Author(s)
      Kuwasako K, Kitamura K, Nagata S, Hikosaka T, Kato J.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 392 Pages: 380-385

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Plasma and tissue levels of proangiotensin-12 and components of the renin-angiotensin system (RAS) following low- or high-salt feeding in rats.2010

    • Author(s)
      Nagata S, Kato J, Kuwasako K, Kitamura K.
    • Journal Title

      Peptides

      Volume: 31 Pages: 889-892

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Stromal cell biology : a way to understand the evolution of cardiovascular diseases.2010

    • Author(s)
      Tsuruda T, Imamura T, Hatakeyama K, Asada Y, Kitamura K.
    • Journal Title

      Circ J

      Volume: 74 Pages: 1042-1050

    • NAID

      10026474117

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] Adrenomedullin does not contribute toward the development of abdominal aortic aneurysm in mice2013

    • Author(s)
      坂元紀陽, 鶴田敏博, 畠山金太, 下澤達雄, 浅田祐士郎, 北村和雄
    • Organizer
      第17回日本心血管内分泌代謝学会学術総会
    • Place of Presentation
      大阪府豊中市
    • Related Report
      2013 Annual Research Report 2013 Final Research Report
  • [Presentation] Glucose metabolism in macrophages contributes to the development of atherosclerosis in apolipoprotein E knockout mice2013

    • Author(s)
      郝異琳, 鶴田敏博, 関田陽子, 坂元紀陽, 畠山金太, 浅田祐士郎, 北村和雄
    • Organizer
      第17回日本心血管内分泌代謝学会学術総会
    • Place of Presentation
      大阪府豊中市
    • Related Report
      2013 Final Research Report
  • [Presentation] Angiotensin II stimulates osteoprotegerin production through angiotensin II type 1 receptor in rats2013

    • Author(s)
      Tsuruda T, Hao Y, Sekita Y, Hatakeyama K, Asada Y, Kitamura K
    • Organizer
      第77回日本循環器学会学術集会
    • Place of Presentation
      神奈川県横浜市
    • Related Report
      2013 Final Research Report
  • [Presentation] Angiotensin II stimulates osteoprotegerin production through angiotensin II type 1 receptor in rats.2013

    • Author(s)
      Tsuruda T, Hao Y, Sekita Y, Hatakeyama K, Asada Y, Kitamura K.
    • Organizer
      第77回日本循環器学会学術集会
    • Place of Presentation
      神奈川県、横浜市
    • Related Report
      2012 Annual Research Report
  • [Presentation] Dysregulation of RANTES to Interleukin-10 is Associated with the Enlargement of Abdominal Aorta in Aged-Apolipoprotein E Knockout Mice2012

    • Author(s)
      Sakamoto S, Tsuruda T, Kitamura K
    • Organizer
      第76回日本循環器学会学術集会
    • Place of Presentation
      福岡県福岡市
    • Year and Date
      2012-03-16
    • Related Report
      2013 Final Research Report
  • [Presentation] Dysregulation of RANTES to Interleukin-10 is Associated with the Enlargement of Abdominal Aorta in Aged-Apolipoprotein E Knockout Mice2012

    • Author(s)
      Sakamoto S, Tsuruda T, Kitamura K
    • Organizer
      第76回日本循環器学会学術集会
    • Place of Presentation
      福岡
    • Year and Date
      2012-03-16
    • Related Report
      2011 Annual Research Report
  • [Presentation] educed fractional shortening of right ventricular outflow tract is associated with adverse outcome in patients with left ventricular dysfunction2012

    • Author(s)
      Tsuruda T, Yamaguchi M, Furukawa K, Ideguchi T, Kawagoe J, Onitsuka H, Ishikawa T, Kitamura K
    • Organizer
      American Heart Association. Scientific Sessions 2012
    • Place of Presentation
      Los Angeles,USA
    • Related Report
      2013 Final Research Report
  • [Presentation] Angiotensin II-dependent osteoprotegerin production in murine and human heart2012

    • Author(s)
      Tsuruda T, Imamura T, Masuyama H, Sekita Y, Koyama S, Ideguchi T, Kawagoe J, Onitsuka H,Ishikawa T, Date H, Hatakeyama K, Asada Y, Kitamura K
    • Organizer
      European Society of Cardiology Congress 2012
    • Place of Presentation
      Munch,Germany
    • Related Report
      2013 Final Research Report
  • [Presentation] Reduced fractional shortening of right ventricular outflow tract is associated with adverse outcome in patients with left ventricular dysfunction.2012

    • Author(s)
      Tsuruda T, Yamaguchi M, Furukawa K, Ideguchi T, Kawagoe J, Onitsuka H, Ishikawa T, Kitamura K.
    • Organizer
      American Heart Association. Scientific Sessions 2012.
    • Place of Presentation
      Los Angeles, Calif, USA
    • Related Report
      2012 Annual Research Report
  • [Presentation] Angiotensin II-dependent osteoprotegerin production in murine and human heart.2012

    • Author(s)
      Tsuruda T, Imamura T, Masuyama H, Sekita Y, Koyama S, Ideguchi T, Kawagoe J, Onitsuka H, Ishikawa T, Date H, Hatakeyama K, Asada Y, Kitamura K.
    • Organizer
      European Society of Cardiology Congress 2012.
    • Place of Presentation
      Munch, Germany
    • Related Report
      2012 Annual Research Report
  • [Presentation] 動脈硬化進展における血管外膜の炎症 : アポリポプロテインE欠損マウスでの検討2011

    • Author(s)
      坂元紀陽, 鶴田敏博, 北村和雄
    • Organizer
      第7回西日本血管・機能研究会
    • Place of Presentation
      福岡県福岡市
    • Year and Date
      2011-08-06
    • Related Report
      2013 Final Research Report
  • [Presentation] 動脈硬化進展における血管外膜の炎症:アポリポプロテインE欠損マウスでの検討2011

    • Author(s)
      坂元紀陽、鶴田敏博、北村和雄
    • Organizer
      第7回西日本血管・機能研究会
    • Place of Presentation
      福岡
    • Year and Date
      2011-08-06
    • Related Report
      2011 Annual Research Report
  • [Presentation] Age dependent and regional difference of Inflammatory responses in the development of atherosclerosis in apolipoprotein E knockout mice2011

    • Author(s)
      Sakamoto S, Tsuruda T, Kitamura K
    • Organizer
      The 60th American College of Cardiology (Annual Scientific Session 2011)
    • Place of Presentation
      New Orleans,USA
    • Year and Date
      2011-04-04
    • Related Report
      2013 Final Research Report
  • [Presentation] Age dependent and regional difference of Inflammatory responses in the development of atherosclerosis in apolipoprotein E knockout mice2011

    • Author(s)
      Sakamoto S, Tsuruda T, Kitamura K
    • Organizer
      The 60th American College of Cardiology (Annual Scientific Session 2011)
    • Place of Presentation
      New Orleans, USA
    • Year and Date
      2011-04-04
    • Related Report
      2011 Annual Research Report
  • [Presentation] Interaction between receptor activity-modifying proteins (RAMPs) and G-protein-coupled receptors and the function of the C-terminal tail of calcitonin receptor-like receptor in complex with RAMP22010

    • Author(s)
      Kuwasako K, Kitamura K, Nagata S, Hikosaka T, Kato J
    • Organizer
      7th International Symposia on the CGRP Family; CGRP, Adrenomedullin, Amylin, Intermedin and Calcitonin
    • Place of Presentation
      Queenstown, New Zealand
    • Year and Date
      2010-08-31
    • Related Report
      2013 Final Research Report
  • [Presentation] Interaction between receptor activity-modifying proteins (RAMPs) and G-protein-coupled receptors and the function of the C-terminal tail of calcitonin receptor-like receptor in complex with RAMP2.2010

    • Author(s)
      Kuwasako K, Kitamura K, Nagata S, Hikosaka T, Kato J
    • Organizer
      7^<th> International Symposia on the CGRP Family ; CGRP, Adrenomedullin, Amylin, Intermedin and Calcitonin
    • Place of Presentation
      Queenstown, New Zealand
    • Year and Date
      2010-08-31
    • Related Report
      2010 Annual Research Report
  • [Book] ストローマからみた心血管病.「序章」2013

    • Author(s)
      北村和雄, 鶴田敏博
    • Publisher
      循環器内科
    • Related Report
      2013 Final Research Report
  • [Book] ストローマからみた心血管病.「ストローマをターゲットとした心血管病の治療」2013

    • Author(s)
      鶴田敏博, 北村和雄
    • Publisher
      循環器内科
    • Related Report
      2013 Final Research Report
  • [Book] Mast cell density and distribution in human abdominal aortic aneurysm, Etiology, Pathogenesis and Pathophysiology of Aortic Aneurysms and Aneurysm Rupture(Reinhart Grundmann (Ed.))2011

    • Author(s)
      Sakamoto S, Tsuruda T, Hatakeyama K, Sekita Y, Imamura T, Asada Y and Kitamura K
    • URL

      http://www.intechopen.com/articles/show/title/mast-cell-density-and-distribution-in-human-abdominal-aortic-aneurysm

    • Related Report
      2013 Final Research Report
  • [Book] 炎症と動脈硬化. マクロファージ・血管構築細胞群2011

    • Author(s)
      鶴田敏博, 畠山金太, 北村和雄
    • Publisher
      日本臨床
    • Related Report
      2013 Final Research Report
  • [Book] 炎症・免疫からみた心血管病. 腹部大動脈瘤形成と炎症2011

    • Author(s)
      鶴田敏博, 坂元紀陽, 北村和雄
    • Publisher
      循環器内科
    • Related Report
      2013 Final Research Report
  • [Book] 炎症と動脈硬化.マクロファージ・血管構築細胞群2011

    • Author(s)
      鶴田敏博、畠山金太, ほか
    • Total Pages
      5
    • Publisher
      日本臨床社
    • Related Report
      2010 Annual Research Report
  • [Book] 大動脈疾患-大動脈解離と胸腹部大動脈瘤:診断と治療の進歩I病因と病態生理3.分子機構と新展開 2)マスト細胞と大動脈疾患 日本内科学会雑誌2010

    • Author(s)
      鶴田敏博, 畠山金太, 北村和雄
    • Related Report
      2013 Final Research Report
  • [Patent(Industrial Property Rights)] 動脈硬化の検査方法2012

    • Inventor(s)
      北村和雄, 他3名
    • Industrial Property Rights Holder
      宮崎大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2012-04-03
    • Related Report
      2013 Final Research Report
  • [Patent(Industrial Property Rights)] マトリックスメタロプロテアーゼ活性抑制組成物2010

    • Inventor(s)
      鶴田敏博
    • Industrial Property Rights Holder
      宮崎大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2010-08-24
    • Related Report
      2013 Final Research Report
  • [Patent(Industrial Property Rights)] マトリックスメタロプロテアーゼ活性抑制組成物2010

    • Inventor(s)
      鶴田敏博
    • Industrial Property Rights Holder
      宮崎大学
    • Industrial Property Number
      2010-187078
    • Filing Date
      2010-08-24
    • Related Report
      2010 Annual Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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