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Organculture as a new model of atherosclerosis

Research Project

Project/Area Number 09660315
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Basic veterinary science/Basic zootechnical science
Research InstitutionThe University of Tokyo

Principal Investigator

OZAKI Hiroshi  The University of Tokyo, Graduate School od agricultural and life sciences, Associate professor, 大学院・農学生命科学研究科, 助教授 (30134505)

Co-Investigator(Kenkyū-buntansha) SATO Koichi  The University of Tokyo, Graduate School od agricultural and life sciences, Assi, 大学院・農学生命科学研究科, 助手 (90205914)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1998: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1997: ¥2,500,000 (Direct Cost: ¥2,500,000)
KeywordsVascular smooth muscle / PDGF / Fetal bovine serum / interleukin-IB / organ culfure / 動脈硬化
Research Abstract

The purpose of this study is to develop new experimental model of a vascular atherosclerosis. For this purpose, we utilized a vascular organ culture system, rather than cultured endothelial cells, which has the advantages to obtain the conditions that better preserves tissue architecture, cell-to-cell interactions, the extracellular matrix, and the morphology and function of differentiated cells and thereby to reproducibly study behavior of the whole tissue in response to environmental stimuli. We tested the effect of tnree agents, interleukin-1B, fetal bovine serum (FBS) ana platelet derived growth factor (PDGF), which are assumed to be related to the vascular growth related disease. The results obtained are follows.
1) We first demonstrated that Interleukin-1B relaxes vascular smooth muscle by the NO-dependent and independent mechanisms (Takizawa et aI. : Eur. J.Pharmacol. 330 : 143-150, 1997). As for the NO-independent mechanism, we further revealed that membrane hyperpolarization due to activation of ATP-sensitive K channels may partly be responsible for it.
2) Chronic treatment with FBS markedly decreased the endothelial NO-dependent relaxation in rabbit mesenteric artery. Total mRNA for endothelial NO synthase were also reduced. PDGF showed similar results with FBS.These results suggest that growth activation of rabbit mesenteric artery decreases endothelial NO synthase mRNA, reduces NO production and impairs endothelium-dependent relaxation.
These results suggest that organ culture is a useful method for studying the mechanism of
vascular growth related disease.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (23 results)

All Other

All Publications (23 results)

  • [Publications] YAMAWAKI, H. et, al: "Impairment of endothelium dependent relaxation following incubation of arteries with FBS." Eur.J.Pharmacol.366. 237-242 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] KARAKI, H. et, al: "Calcium movements, distribution, and functions in smooth muscle." Pharmacol.Rev.49. 157-230 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] TAKIZAWA, S., OZAKI, H. and KARAKI, H.: "Interleukin-1 β-induced nitric oxide-dependent and - independent inhibition of vascular smooth muscle." Eur.J.Pharmacol.330. 143-150 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] IZUMI, M. et, al: "Cicletanine-induced decreases in cytosolic Ca2+ level and contraction in vascular smooth muscle." Jpn.J.Pharmacol.76. 57-63 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] YOSHIMOTO, Y. et, al: "The relaxant effect of adrenomedullin and calcitonin gene-related peptide on contractions of the rat aorta and porcine coronary artery." Br.J.Pharmacol.123. 1645-1654 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 尾崎 博、山脇英之、佐藤晃一、堀 正敏、唐木英明、: "増殖性変化を起こした血管組織の内皮機能ならびに平滑筋収縮性の変化 : 器官培養法による検討" 日薬理誌. 112. 63-67 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] TAKIZAWA, S., et, al: "Possible Involvement of K^+ channel Opening to the Interleukin-1β-Induced Inhibition of Vascular Smooth Muscle Contraction." J.Vet.Med.Sci.(In press.). (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Karai, H., Ozaki, H., Hori, M., Mitsui-Saito, M., Amano, K., Harada, K., Miyamoto, S., Nakazawa, H., Won, K.-J.and Sato, K.: "Calcium movements, distribution, and functions in smooth muscle." Pharmacol.Rev.49. 157-230 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takizawa, S., Ozaki, H.and Karaki, H. :"Interleukin-1beta-induced nitric oxide-dependent and-independent inhibition of vascular smooth muscle." Eur.J.Pharmacol.330. 143-150 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Izumi, M., Mitsui-Sato, M., Ozaki, H.and Karai, H. :"Cicletanine-induced decreases in cytosolic Ca^<2+> level and contraction in vascular smooth muscle." Jpn.J.Pharmacol.76 :. 57-63 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yoshimoto, Y., Hori, M., Ozaki, H.and Karai, H, :"The relaxant effect of adrenomedullin and calctonin gene-reated peptide on contractions of the rat aorta and porcine cornary artery." Br.J.Pharmacol.123. 1645-1654 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takizawa, S., Ozaki, H.and Karai, H. :"Possible Involvement of K^+ channel Opening to the Interleukin-1beta-Inhibition of Vascular Smooth Muscle Contraction." J.Vet.Med.Sci.(inpress). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yamawaki, H., Sato, K., Hori, M., Ozaki, H., Nakamura, S., Nakayama, H., Doi, K.and Karaki, H.: "Inpairment of endothelium dependent relaxation following incubation of arteries with FBS." Eur.J.Pharmacol.366. 237-242 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] AMANO,K.et,al: "Palytoxin-induced increase in endothelial Ca2+ concentration in the rabbit aortic valve." Naunyn-Schmiedeberg's Arch Pharmacol.355. 751-758 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] KARAKI,H.et,al: "Calcium movements,distribution,and functions in smooth muscle." Pharmacol.Rev.49. 157-230 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] TAKIZAWA,S.,OZAKI,H.and KARAKI,H.: "Interleukin-1β-induced nitric oxide-dependent and - independent inhibition of vascular smooth muscle." Eur.J.Pharmacol.330. 143-150 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] IZUMI,M.et,al: "Cicletanine-induced decreases in cytosolic Ca2+ level and contraction in vascular smooth muscle." Jpn.J.Pharmacol.76. 57-63 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] YOSHIMOTO,Y.et,al: "The relaxant effect of adrenomedullin and calcitonin gene-related peptide on contractions of the rat aorta and porcine coronary artery." Br.J.Pharmacol.123. 1645-1654 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 尾崎 博、山脇英之、佐藤晃一、堀 正敏、唐木英明、: "増殖性変化を起こした血管組織の内皮機能ならびに平滑筋収縮性の変化:器官培養法による検討" 日薬理誌. 112. 63-67 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] TAKIZAWA,S.,OZAKI,H.and KARAKI,H: "Possible Involvement of K^+ channel Opening to the Interleukin-1β-Induced Inhibition of Vascular Smooth Muscle Contraction." J.Vet.Med.Sci.in press.

    • Related Report
      1998 Annual Research Report
  • [Publications] YAMAWAKI,H.et al: "Impairment of endothelium dependent relaxation following incubation of arteries with FBS." Eur.J.Pharmacol.in press. (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Karaki et al.: "Calcium Movements,Distribution and Functions in Smooth Muscle" Pharmacological Reviews. 49. 157-230 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Takizawa, Ozaki and Karaki: "Interleukin-1β-induced,nitric oxide-dependent and -independent inhibition of vascular smooth muscle contraction" European Journal of Pharmacology. 330. 143-150 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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