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Genomic characteristics of pulmonary circulation in high-altitude living animal

Research Project

Project/Area Number 16406026
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section海外学術
Research Field Respiratory organ internal medicine
Research InstitutionUniversity of Fukui

Principal Investigator

ISHIZAKI Takeshi  University of Fukui, Faculty of Medicine, Professor, 医学部, 教授 (80151364)

Co-Investigator(Kenkyū-buntansha) AMESHIMA Shingo  University of Fukui Hospital, Lecturer, 医学部附属病院, 講師 (60262614)
MATSUKAWA Shigeru  University of Fukui, Centers for Advanced Research Support, Associate Professor, 助教授 (00092809)
SAKAI Akio  Shinshu University, Graduate School of Medicine, Associate Professor, 大学院医学研究科, 助教授 (70020758)
MIZUNO Shirou  University of Fukui, Faculty of Medicine, Assistant Professor, 医学部, 助手 (80397281)
Project Period (FY) 2004 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥12,600,000 (Direct Cost: ¥12,600,000)
Fiscal Year 2006: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥4,400,000 (Direct Cost: ¥4,400,000)
Fiscal Year 2004: ¥4,700,000 (Direct Cost: ¥4,700,000)
KeywordsYak / Pulmonary Circulation / eNOS / DDAH / ADMA / ET-1 / 低酸素適応 / 高地適応 / 極限高地生息動物 / ナキウサギ / HIF1α / ET1
Research Abstract

We investigated the pulmonary characteristics of Yak, a high-altitude adapted animal that is resistant to hypoxia-induced pulmonary hypertension, cor pulmonale in terms of hypoxia-responsible genomic products such as eNOS, DDAH (dimethylarginine dimethylaminohydrolase), ADMA (asymmetrically methylated Arginine) and ET-1.
Results;
1. The protein expression of eNOS, and protein expression and activity of DDAH in yak's lung tissue were more elevated than that of control cow. However, the degree of protein expression of DDAH in the Kidney was the same in both animals.
2. The plasma level of ADMA was 5-times higher in Yak compared to that of cow. Among cow groups, high-altitude living one has 4-times high ADMA level compared to that of low-altitude living one.
3. The plasma ET-1 level was higher in Yak than in cow.
These results suggest that wild yak's lung has augmented eNOS protein and augmented DDAH activity compared to cow. On the contrary, the animal has elevated plasma ADMA and ET-1 suggesting that the balance of vasodilators and vasoconstrictors are up-regulated. Although we did not assess transpulmonary difference of plasma ADMA and ET-1, it appears that Yak's lung preferentially expressed protective NO mechanism(s) which may result the relatively low pulmonary arterial pressure despite of high-altitude. It may induce a good suggestion from the animal study if think about hypoxic-air induced pulmonary hypertension and chronic respiratory failure in clinical medicine in terms of pathogenesis and treatment strategy.

Report

(4 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • Research Products

    (19 results)

All 2007 2006 2005

All Journal Article (19 results)

  • [Journal Article] Current opinion低酸素と肺高血圧 肺血管リモデリングを中心に2007

    • Author(s)
      水野史朗, 石崎武志
    • Journal Title

      呼吸と循環 55

      Pages: 105-109

    • NAID

      40015241052

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Current opinion. : Hypoxia and pulmonary hypertension, Remodeling of pulmonary vessel2007

    • Author(s)
      Mizuno S, Ishizaki T.
    • Journal Title

      Respiration and Circulation 55

      Pages: 105-109

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Current opinion 低酸素と肺高血圧 肺血管リモデリングを中心に2007

    • Author(s)
      水野史朗, 石崎武志
    • Journal Title

      呼吸と循環 55

      Pages: 105-109

    • NAID

      40015241052

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Hypoxia-induced proliferation of human pulmonary arterial smooth muscle cell is involved in the suppression of cyclin-dependent kinase inhibitors, P21, P27 and P53.2006

    • Author(s)
      Ishizaki T, et al.
    • Journal Title

      High Altitude Medicine and Biology Advanced Research Workshop Abstract book

      Pages: 12-12

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] 低酸素性肺血管収縮2006

    • Author(s)
      石崎武志
    • Journal Title

      Annual Review 呼吸器

      Pages: 107-112

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Rho-Kinase Mediates Hypoxia-Induced Down-Regulation of Cyclin Dependent Kinase Inhibitor p272006

    • Author(s)
      M Kadowaki, et al.
    • Journal Title

      American Journal of Respiratory and Critical Care Medicine ABSTRACTS ISSUE 2

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] 高地生息動物,ヤク肺Dimethylarginine-dimethyl-amino-hydrolase(DDAH)活性2006

    • Author(s)
      石崎武志, 他
    • Journal Title

      Integrated Pulmonary Circulation Research Abstract issue 6

      Pages: 1-2

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Hypoxia-induced proliferation of human pulmonary arterial smooth muscle cell is involved in the suppression of cyclin-dependent kinase inhibitors, P21, P27 andP53.2006

    • Author(s)
      Ishizaki T, Mizuno S, Kadowaki M, Uesaka D, Umeda Y, Morikawa M, Nakanishi M, Demura Y, Ameshima S.
    • Journal Title

      High Altitude Medicine and Biology Advanc Research Workshop abstract book P12

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] vasoconstriction2006

    • Author(s)
      Ishizaki T.Hypoxic pulmonary
    • Journal Title

      Annual Review Respirology

      Pages: 107-112

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Rho-Kinase Mediates Hypoxia-Induced Down-Regulation of Cyclin Dependent Kinase Inhibitor p272006

    • Author(s)
      M Kadowaki, S Mizuno, D Uesaka, Y Demura, S Ameshima, I Miyamori, T Ishizaki.
    • Journal Title

      American Journal of Respiratory and Critical Care Medicine abstract issue2 A757

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Lung dimethylarginine-dimethyl-amino-hydrolase (DDAH)activity of high-altitude adapted animal, Yak.2006

    • Author(s)
      Ishizaki T, Sakai A, Mizuno S, B. KojonazaroV, A. Aldashev.
    • Journal Title

      Integrated Pulmonary Circulation Research Abstract issue 6 P1-2

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Hypoxia-induced proliferation of human pulmonary arterial smooth muscle cell is involved in the suppression of cyclin-dependent kinase inhibitors, P21, P27 and P53.2006

    • Author(s)
      Ishizaki T, Mizuno S, Kadowaki M, Uesaka D, Umeda Y, Morikawa M, Nakanishi M, Demura Y, Ameshima S
    • Journal Title

      High Altitude Medicine and Biology Advanced Research Workshop Abstract book

      Pages: 12-12

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Rho-Kinase Mediates Hypoxia-Induced Down-Regulation of Cyclin Dependent Kinase Inhibitor p272006

    • Author(s)
      M Kadowaki, S Mizuno, D Uesaka, Y Demura, S Ameshima, I Miyamori, T Ishizaki
    • Journal Title

      American Journal of Respiratory and Critical Care medicine ABSTRACTS ISSUE 2

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 高知生息動物、ヤク肺Dimethylarginine-dimethyl-amino-hydrolase (DDAH)活性2006

    • Author(s)
      石崎武志, 酒井秋男, 水野史朗, B.Kojonazarov, A.Aldashev.
    • Journal Title

      Integrated Pulmonary Circulation Research Abstract issue 6

      Pages: 1-2

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Nitric oxide inhibitor altitude-dependently elevates pulmonary arterial pressure in high-altitude adapted yaks.2005

    • Author(s)
      Ishizaki T, et al.
    • Journal Title

      Respir Physiol & Neurobiol. 146

      Pages: 225-230

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] 特集 低酸素と生体 低酸素における肺組織・細胞の応答2005

    • Author(s)
      水野史朗, 石崎武志
    • Journal Title

      呼吸と循環 53

      Pages: 1119-1125

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Nitric oxide inhibitor altitude-dependently elevates pulmonary arterial pressure in high-altitude adapted yaks.2005

    • Author(s)
      Ishizaki T, Koizumi T, Ruan Z, Wang Z, Chen Q, Sakai A.
    • Journal Title

      Respir Physiol & Neurobio1 146

      Pages: 225-230

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Hypoxia and biological body : Lung tissue and cellular response to hypoxia2005

    • Author(s)
      Mizuno S, Ishizaki T.
    • Journal Title

      Respiration and Circulation 53

      Pages: 1119-1125

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Nitric Oxide inhibitor altitude-dependently elevates pulmonary arterial pressure in high-altitude adapted yaks2005

    • Author(s)
      Takeshi I, Tomonori K, Zong HR, Qiu HC, Zhan GW, Xiao QW, AKio S
    • Journal Title

      Respiratory physiology & Neurobiology 145(3)(Available On line)

    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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