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Investigation of Regression of Atherosclerotic Lesion through Regulation of Nitric Oxide Related Responses -Treatment by Gene Transfer of Nitric Oxide Synthase-

Research Project

Project/Area Number 09470166
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionNagoya University

Principal Investigator

IGUCHI Akihisa  Nagoya University, School of Medicine, Professor, 医学部, 教授 (20109763)

Co-Investigator(Kenkyū-buntansha) SAKUMA Ichiro  Hokkaido University, School of Medicine, Assistant Professor, 医学部, 講師 (40260393)
WATANABE Yasuo  School of Medicine, Assistant Professor, 医学部, 講師 (10273228)
HAYASHI Toshio  School of Medicine, Research Associate, 医学部, 助手 (80303634)
Project Period (FY) 1997 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥11,200,000 (Direct Cost: ¥11,200,000)
Fiscal Year 1999: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1998: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 1997: ¥4,800,000 (Direct Cost: ¥4,800,000)
KeywordsEndothelial nitric oxide synthase / Inducible nitric oxide synthase / Gene Therapy / Atherosclerosis / Adeno Virus / 一酸化窒素 / 動脈硬化退縮 / 遺伝子導入 / 血管内超音波 / 一酸化窒素合成酵素 / 構造機能解析
Research Abstract

We determined the effect of endothelial and inducible nitric oxide synthase (eNOS, iNOS) gene transfer using adenovirus vector on the advanced lesion of atherosclerosis. We prepared adenovirus vector of eNOS and iNOS cDNA. The abdominal aortae of 40 male and oophorectomized female rabbits were injured by balloon catheter and they were fed with HCD [standard diet and 1% cholesterol] for 12 weeks. After treatment, we made sure the size and character of atherosclerosis in thoracic (HCD induced) and abdominal (endothelial injury plus HCD) aorta using IVUS (intra vascular ultra sonography). Then, we transferred gene of eNOS, iNOS and eNOS plus iNOS onto atherosclerotic lesion of thoracic and abdominal aorta using dispatch blood flow reserved catheter. As the control, cDNA vector of β-galactosidase was transferred. After 3 and 7 days of gene transfer, the change of size and character of atherosclerosis in thoracic and abdominal aorta was examined using IVUS, and then, animals were sacrificed … More and examined as below. Basal and stimulated NO release was estimated by an NO selective electrode as well as vascular response and the plasma NO metabolites. Surface involvement and area occupied by atherosclerotic lesion were also evaluated. An immunohistochemical study was done. The area occupied by macrophage derived foam cells was numbered. HCD mediated increased plasma lipid levels were not affected by gene transfer of each vector. Not only atherosclerosis in the thoracic aorta but also severe atherosclerosis in the abdominal aorta was partially improved by eNOS and iNOS gene transfer. The acetylcholine-induced NO-mediated relaxation was severely impaired in HCD supplemented balloon injured rabbits. The impaired abdominal aortic relaxation of balloon injured and atherogenic diet supplemented rabbits was slightly restored by eNOS and iNOS gene transfer. The above results suggest that gene transfer of eNOS and iNOS could regress the advanced lesion of severe mechanisms and more effective combined virus vector will be elucidated from now. Less

Report

(4 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • 1997 Annual Research Report
  • Research Products

    (28 results)

All Other

All Publications (28 results)

  • [Publications] Hayashi T., Iguchi A. 他3名: "Physiological concen*m*on of 17β****diol re**nts the prog**ion of severe ******len*is induced by cholemen**diet plus b*llo** injury vi* NO."Arterioscler Thromb Vasc Biol.. (印刷中). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hayashi T., Iguchi A. 他6名: "dehydrosplandn***ne re***ds *the***l**mls fom**** through the co*emion to e*rogen The po****e role of **s*oxl**"Arterioscler Thromb Vasc Biol.. (印刷中). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hayashi T., Iguchi A. 他3名: "Endothellum-dependent relax*llon of **bbit *theromolensic *o*s was not res*oed **nin* if hyper*lpidemia The poss*** role of p*roxynl***"Atherrosclerosis. 147. 349-367 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hayashi T., Iguchi A. 他2名: "E** no* replacement improves end**hellm *une**on and bone mineral density in elderly women"J. Gerontology. (印刷中). (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kano H., Hayashi T. 他4名: "A HMG-Coa reductase inhibitor improved regression of *hero**l*nm* without *ff**ing serum lipid lev*la-Relevance of upregu**ion of *NOS"Biochem. Biophys. Res. Commun.. 259. 414-419 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hayashi T., Esaki T., Mutoh, E., Iguchi A. 他4名: "Recent Advances in Ni*ric Oxide Research"Springer-Verlag 社. (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hayashi T, Iguchi A. et al.: "Physiological concentration of 17β estradiol retards the progression of severe atherosclerosis induced by cholesterol diet plus balloon injury via NO"Arterioscler Thromb Vasc Biol. (in press). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hayashi T, Iguchi A. et al.: "Dehydroepiandrosterone retards atherosclerosis formation through the conversion to estrogen -The possible role of nitric oxide-"Arterioscler Thromb Vasc Biol ; 20. (in press). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hayashi T, Iguchi A. et al.: "Endothelium-dependent relaxation of rabbit atherosclerotic aorta was not restored by control of hyperlipidemia-The possible role of peroxynitrite"Atherosclerosis. 147. 349-367 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hayashi T, Iguchi A. et al.: "Estriol replacement improves endothelial function and bone mineral density in elderly women"J gerontol. (in press). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kano H, Hayashi T, Iguchi A. et al.: "A HMG-CoA reductase inhibitor improved regression of atherosclerosis without affecting serum lipid levels - Relevance of upregulation of eNOS"Biochem Biophys Res Commun. 259. 414-419 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hayashi T, Iguchi A. et al.: "Estrogen and Nitric Oxide : Possible mechanism of anti-atherosclerotic effect of Research estrogen via isoforms of nitric oxide synthase"Recent Advance in Nitric Oxide (A Kitabatake, I. Sakuma eds.). 67-82 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hayashi T.Iguchi A.他3名: "Physiological concentration of 17β estradiol retards the progression of severe atherosclerosis induced by cholesterol diet plus balloon injury via NO."Arterioscler Thromb Vasc Biol. (印刷中). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hayashi T. Iguchi A.他6名: "Dehydro***** retards atheroscrelosis formation through the conversion to estrogen - The possible role of nitric oxide -"Arterioscler Thromb Vasc Biol. (印刷中). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hayashi T.Iguchi A.他3人: "Endothelium-dependent relaxation of rabbit atherosclerotic aorta was not restored by control of hyperlipidemia - The possible role of peroxynitrite"Atherosclerosis. 147. 349-367 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hayashi T.Iguchi A.他2名: "Estriol replacement improves endothelial function and bone mineral density in elderly women"J gerontology. (印刷中). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kano H.Hayashi T.他4名: "A HMG-CoA reductase inhibitor improved regression of atherosclerosis without affecting serum lipid levels-Relevance of upregulation of eNOS."Biochem Biophys Commun. 259. 414-419 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hayashi T.Esaki T.Mutoh E.Iguchi A.他4名: "Recent Advances in Nitric Oxide Research"Springer-Verlagm 社. (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hayashi T,and Iguchi A.: "Physiological concentration of 17β-estradiol inhibita the effect of inducible nitric oxide synthase in macrophage cell line:J774 by receptor mediated system." J Cardiovascular Pharmacology. 31. 292-298 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kanda S,Hayashi T,and Iguchi A.: "Induction of macrophage VEGF in response to oxidized LDL and VEGF accumulation in human atherosclerotic lesions." Arteriosclerosis,Thrombosis,and Vascular Biology.18. 1188-1196 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hayashi T,and Iguchi A.: "Dehydroepiandrosterone retards atherosclerosis formation partially through the conversion to estrogen-the possible role of nitric oxide-" Nitric Oxide 2,. 2. 115-117 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hayashi T,Iguchi A.: "Nipradilol:A β-adrenoceptor antagonist with nitric oxide-releasing action." Cardiovase Drug Reviews. 16. 212-236 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hayashi T,Muto E,and Iguchi A.: "Estrogen and Nitric Oxide:Possible mechanism of anti-atherosclerotic effect of estrogen via isoforms of nitric oxide synthase" Recent Advances in Nitric Oxide Research. 67-82 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hayashi T, Iguchi A et al: "Inducible Nitric Oxide Synthase is expressed in atherosclerotic lesions of cholesterol-fed rabbits." Atherosclerosis. 128. 39-46 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Hayashi T, Iguchi A et al: "The β-adrenoreceptor antagonist, nipradiol, preserves the endothelial nitric oxide response in atherosclerotic vessels of rabbit." Life Sciences. 61. 1379-1387 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Hayashi T, Iguchi A et al: "The role of estrogen in atherosclerosis ; Estrogen increases endothelial nitric oxide and inhibits inducible nitiric oxide by a receptor mediated system." Gerontology. 43. 24-34 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Hayashi T, Iguchi A et al: "Physiological concentration of 17β-estradiol inhibits the synthesis of inducible nitric oxide synthase in macrophages." J Cardiovascular Pharmacology. (in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Hayashi T, Iguchi A et al: "Nipradilol ; β-adrenergic blocker with NO releasing activity" J Cardiovascular Drug Review. (in press). (1998)

    • Related Report
      1997 Annual Research Report

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

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