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Molecular mechanisms of cerebral aneurysmal formation

Research Project

Project/Area Number 13307043
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Cerebral neurosurgery
Research InstitutionKyoto University

Principal Investigator

HASHIMOTO Nobuo  Kyoto University, Graduate School of Medicine, Professor, 医学研究科, 教授 (40135570)

Co-Investigator(Kenkyū-buntansha) KUME Noriaki  Kyoto University, Graduate School of Medicine, Assistant Professor, 医学研究科, 講師 (20252455)
KITA Toru  Kyoto University, Graduate School of Medicine, Professor, 医学研究科, 教授 (60161460)
NOZAKI Kazuhiko  Kyoto University, Graduate School of Medicine, Assistant Professor, 医学研究科, 助教授 (90252452)
NAGATA Kazuhiro  Kyoto University, Institute for Frontier Medical Sciences, Professor, 再生医科学研究所, 教授 (50127114)
Project Period (FY) 2001 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥53,040,000 (Direct Cost: ¥40,800,000、Indirect Cost: ¥12,240,000)
Fiscal Year 2003: ¥11,570,000 (Direct Cost: ¥8,900,000、Indirect Cost: ¥2,670,000)
Fiscal Year 2002: ¥19,110,000 (Direct Cost: ¥14,700,000、Indirect Cost: ¥4,410,000)
Fiscal Year 2001: ¥22,360,000 (Direct Cost: ¥17,200,000、Indirect Cost: ¥5,160,000)
Keywordscerebral aneurysmal / iNOS / endothelium / MMP / gene / 動物モデル / 血行力学的ストレス / 高血圧 / ラット / マウス / hemodynamic stress
Research Abstract

The pathogenesis of cerebral aneurysm has not been-fully understood. We have developed experimental cerebral aneurysmal models in rats and mice and analyzed expressed proteins and messenger RNAs during the process of cerebral aneurismal formation. We confirmed the decrease in eNOS in the endothelium and increase in iNOS in the smooth muscle during the process, and demonstrated that an inhibitor of iNOS and the disruption of iNOS gene inhibited the aneurysmal formation. We also demonstrated increased active MMP-2 and 9 during the process and the knockout of MMP-9 decreased the formation of cerebral aneurysm. We also detected by PCR the expression of specific molecules which are related to vascular remodeling. Finally we analyzed the candidate genes which had high linkage to aneurysmal formation in highly-aggregated Japanese families.

Report

(4 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (21 results)

All Other

All Publications (21 results)

  • [Publications] Takagi Y, et al.: "Increased expression of phosphorylated JNK and phosphorylated c-Jun in human cerebral aneurysms"Neurosurgery. 51. 997-1002 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Morimoto M, et al.: "Mouse model of cerebral aneurysm : experimental induction by renal hypertension and local hemodynamic changes"Stroke. 33. 1911-1915 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yamada S, et al.: "Absence of linkage of familial intracranial aneurysms to 7q11 in highly aggregated Japanese families"Stroke. 34. 892-900 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kawanabe Y, et al.: "Molecular mechanism for endothelin-1-induced stress-fiber formation"Molecular Pharmacol. 61. 277-284 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sadamasa N, et al.: "Disruption of gene for inducible nitric oxide synthase reduces progression of cerebral aneurysms"Stroke. 34. 2980-2984 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 定政信猛 他: "脳動脈瘤の分子生物学"脳と循環. 7. 65-69 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kawanabe Y, Okamoto, Y, Nozaki K, Hashimoto N, Miwa S, Masaki T: "Molecular mechanism for endothelin-1-induced stress-fiber formation: analysis of G proteins using a mutant Endothelin A receptor"Molecular Pharmacol. 61. 277-284 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takagi Y, Ishikawa M, Nozaki K, Yoshimura S, Hashimoto N: "Increased expression of phosphorylated JNK and phosphorylated c-JUN in human cerebral aneurysms. The role of JNK/c-JUN pathway in apoptosis of vascular wall"Neurosurgery. 51. 997-1002 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Morimoto M, Kume N, Miyamoto S, Mizoguchi A, Nozaki K, Sadariiasa N, Kita T, Hashimoto N: "The roles of MMPs for cerebral aneurysm formation"Kikuchi H., Strategic Medical Science Against Brain Attack, Springer-Verlag (Tokyo). 223-233 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Morimoto M, Miyamoto S, Mizoguchi A, Kume N, Kita T, Hashimoto N: "Mouse model of cerebral aneurysm: experimental induction by renal hypertension and local hemodynamic changes"Stroke. 33. 1911-1915 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Yamada S, Utsunomiya M, Inoue K, Nozaki K, Miyamoto S, Hashimoto N, Takenaka K, Yoshinaga T, Koizumi A: "Absence of linkage of familial intracranial aneurysms to 7q.11 in highly aggregated Japanese families"Stoke. 34. 892-900 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kawanabe Y, Nozaki K, Hashimoto N, Masaki T: "Characterization of Ca2+ channels and G proteins involved in arachidonic acid release by endothelin-1 /endothelin A receptor"Mol Pharmacol. 64. 689-695 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sadamasa N, Nozaki K, Moriwaki T, Hashimoto N: "Disruption of gene for inducible nitric oxide synthase reduces progression of cerebral aneurysms"Stroke. 34. 2980-2984 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sadamasa N. et al.: "Disruption of gene for inducible nitric oxide synthase reduces progression of cerebral aneurysms"Stroke. 34. 2980-2984 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yamada S. et al.: "Absence of linkage of familial intracranial aneurysms to 7q11 in highly aggregated Japanese families"Stroke. 34. 892-900 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Morimoto M et al.: "Mouse model of cerebral aneurysm"Stroke. 33. 1911-1915 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takagi Y et al.: "Increased expression of phosphorylated c-Jun amino-terminal kinase and phosphorylated c-Jun in human cerebral aneurysms"Neurosurgery. 51. 997-1004 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yamada S et al.: "Absence of linkage of familial intracranial aneurysms to 7q11 in highly aggregated Japanese families"Stroke. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Morimoto M et al.: "Strategic medical science against brain attack"Springer-Verlag Tokyo. 294 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] 定政信猛, 野崎和彦, 橋本信夫: "脳動脈瘤の分子生物学"脳と循環. 7. 65-69 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] 定政信猛, 野崎和彦, 橋本信夫: "能動脈瘤と遺伝子-ポストゲノム時代を迎えて-"分子脳血管病. 1. 39-44 (2002)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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