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Role of coupling factor 6 in the pathogenesis of cardiovascular disease

Research Project

Project/Area Number 13670686
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

OSANAI Tomohiro  Hirosaki Univ. Sch. Of Med., 2^<nd>Depart. Of Int. Med., Associate Professor, 医学部, 助教授 (00169278)

Co-Investigator(Kenkyū-buntansha) KAMADA Takaatsu  Hirosaki Univ. Sch. Of Med., 2^<nd>Depart. Of Int. Med., Assistant, 医学部, 助手 (90281930)
OKUMURA Ken  Hirosaki Univ. Sch. Of Med., 2^<nd>Depart. Of Int. Med., Professor, 医学部, 教授 (20185549)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2001: ¥2,200,000 (Direct Cost: ¥2,200,000)
KeywordsMitochondria / Vasoconstrictor / Shear stress / Prostacyclin / Endothelial cells / Coupling factor 6 / Hypertension / Shear atress
Research Abstract

Salt sensitivity of blood presure ins an important risk factor for cardiovascular events. Coupling factor 6 is an endogenous inhibitor of prostacyclin synthesis and a vasoonstrictor. We investigated the role of coupling facor 6 in salt sensitivity in human hypentension.The patients with essential hypertension (EH)(n=30) received a series of normal salt diet (12g salt/day) for 3 days, low salt diet (2g salt) for 7 days, and high salt diet (20-23g salt) for 7 days. Normotensive control subjects (n=27) received normal and low salt diets. The plasma level of coupling factor 6, measured by radioimmunoassay, during normal salt diet was higher in patients with Eh than in normotensive subjects (17.6±1.7 vs 12.8±0.5 ng/ml, p<0.01). Whereas the plasma level of coupling factor 6 was unchanged after salt restriction in normotensive subjects , it was decreased after salt restriction and increased after salt loading inpatients with EH. The percent changes in plasma coupling factor 6 level after salt restriction and loading were positively correlated with those in mean blood pressure (r=0.57, p<0.01). During high salt diet, oral administration of ascorbic acid induced the decrease in plasma levels of coupling factor 6 and 8-epi-prostaglandin F_<2xx> without affecting blood pressure level. The percent changes in plasma coupling factor 6 level were negatively correlated with those in plasma nitric oxide level (r=0.51, p<0.05). These indicate that circulating coupling factor 6 is modulated by salt intake in human hypertension presumably via reactive oxygen species and it may be involved in higher cardiovascular risk in salt sensitivity

Report

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

    (21 results)

All Other

All Publications (21 results)

  • [Publications] Natano T et al.: "Enhanced activity of variant phospholipase C-δ1 protein (R257H) detected in patients with coronary artery spasm"Circulation. 105. 2024-2029 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Osanai T et al.: "Relationship between salt intake, nitric oxide and asymmetric dimethylarginine and its relevance to patients with end-stage renal disease"Blood Purif. 20. 466-468 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Osanai T et al.: "Mitochondrial coupling factor 6 as an endogenous inhibitor of prostacyclin synthesis and an endogenous vasoconstrictor"International Congress Series. 1244. 131-141 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Okuguchi T et al.: "Effect of losartan on nocturnal blood pressure in patients with stroke ; comparison with angiotensin converting enzyme inhibitor"Am J Hypertens. 15. 998-1002 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takahashi K et al.: "Enhanced activities and gene expression of phosphodiesterase types 3 and 4 in pressure-induced congestive heart failure"Heart Vessels. 16. 249-256 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kosugi T et al.: "Phospholipase C activity is enhanced in skin fibroblasts obtained from patients with essential hypertension"J Hypertens. 21(In press). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakano T, Osanai T, Tomita H, Sekimata M, Homma Y, Okumura K.: "Enhanced activity of variant phospholipase C-δ1 protein (R257H) detected in patients with coronary artery spasm"Circulation. 105. 2024-2029 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Osanai T, Fujiwara N, Saitoh M, Sasaki S, Tomita H, Nakamura M, Osawa H, Yamabe H, Okumura K.: "Relationship between salt intake nitric oxide and asymmetric dimethylarginine and its relevance to patients with end-stage renal disease"Blood Purif. 20. 466-468 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Osanai T, Okada S, Saitoh M, Ono H, Magota K, Kodama S, Okumura K.: "Mitochondrial coupling factor 6 as an endogenous inhibitor of prostacy clin synthesis and an endogenous vasoconstrictor"International Congress Series. 1244. 131-141 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Okuguchi T, Osanai T, Fujiwara N, Kato T, Metoki N, Kouta Y, Okumura K.: "Effect of losartan on nocturnal blood pressure in patients with stroke ; comparison with angiotensin converting enzyme inhibitor"Am J Hypertens. 15. 998-1002 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takahashi K, Osanai T, Nakano T, Wakui M, Okumura K.: "Enhanced activities and gene expression of phosphodiesterase types 3 and 4 in pressure-induced congestive heart failure"Heart Vessels. 16. 249-256 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kosugi T, Osanai T, Kamada T, Nakano T, Okumura K.: "Phospholipase C activity is enhanced in skin fibroblasts obtained from patients with essential hypertension"J Hypertens. in press. (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Natano T et al.: "Enhanced activity of variant phospholipase C-δ1 protein (R257H) detected in patients with coronary artery spasm"Circulation. 105. 2024-2029 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Osanai T et al.: "Relationship between salt intake, nitric oxide and asymmetric dimethylarginine and its relevance to patients with end-stage renal disease"Blood Purif. 20. 466-468 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Osanai T et al.: "Mitochondrial coupling factor 6 as an endogenous inhibitor of prostacyclin synthesis and an endogenous vasoconstrictor"International Congress Series. 1244. 131-141 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Okuguchi T et al.: "Effect of losartan on nocturnal blood pressure in patients with stroke; comparison with angiotensin converting enzyme inhibitor"Am J Hypertens. 15. 998-1002 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takahashi K et al.: "Enhanced activities and gene expression of phosphodiesterase types 3 and 4 in pressure-induced congestive heart failure"Heart Vessels. 16. 249-256 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kosugi T et al.: "Phospholipase C activity is enhanced in skin fibroblasts obtained from patients with essential hypertension"J Hypertens. 21(In press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Osanai T et al.: "Mitochondrial coupling factor 6 as a potent endogenous vasoconstrictor"J Clin Invest. 108. 1023-1030 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Osanai T et al.: "Mitochondrial coupling factor 6 is present the surface of human vascular endothelial cells and is released by shear stress"Circulation. 104. 3132-3136 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Osanai T et al.: "Cross talk between Prostacyclin and nitric oxide under shear in smooth muscle cell : role in monocyte adhesion"Am J Physiol Heart Circ Physiol. 281. H177-H182 (2001)

    • Related Report
      2001 Annual Research Report

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

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