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The pivotal role of eNOS uncoupling-induced vascular endothelial dysfunction in cardiovascular diseases

Research Project

Project/Area Number 22790712
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Circulatory organs internal medicine
Research InstitutionKumamoto University

Principal Investigator

YAMAMOTO Eiichiro  熊本大学, 医学部附属病院, 助教 (50573614)

Project Period (FY) 2010 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2010: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords循環器学 / 血管内皮機能
Research Abstract

We previously reported that eNOS uncoupling-induced vascular endothelial dysfunction is closely associated with diastolic heart failure(DHF) in salt-sensitive hypertensive rats. In this study, first, we found that angiotensin II induced eNOS uncoupling via ASK-1 activation and downregulation of GTPCH-I(BH4 producing enzyme) in vitro. Second, in clinical study, we found that peripheral endothelial dysfunction assessed by digital peripheral arterial tonometry, was significantly impaired in human DHF patients. Furthermore, blood BH4 levels tended to be decreased in DHF patients, indicating the involvement of eNOS uncoupling by BH4 downregulation also in human DHF.

Report

(3 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • Research Products

    (30 results)

All 2012 2011 2010

All Journal Article (25 results) (of which Peer Reviewed: 25 results) Presentation (5 results)

  • [Journal Article] Genetic Variants at the 9p21 Locus Contribute to Atherosclerosis through Modulation of ANRIL and CDKN2A/B2012

    • Author(s)
      Congrains A., Yamamoto E., Rakugi H., et al.(20人中6番目)
    • Journal Title

      Atherosclerosis

      Volume: (印刷中)

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Calcium channel blockers, more than diuretics, enhance vascular protective effects of angiotensin receptor blockers in salt-loaded hypertensive rats2012

    • Author(s)
      Yamamoto E., Kim-Mitsuyama S., et al.(10人中1番目)
    • Journal Title

      PLoS One

      Volume: (印刷中)

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Amlodipine enhances amelioration of vascular insulin resistance, oxidative stress, and metabolic disorders by candesartan in metabolic syndrome rats2012

    • Author(s)
      Sueta D., Yamamoto E., Kim-Mitsuyama S., et al, (10人中6番目)
    • Journal Title

      Am J Hypertens

      Volume: (印刷中)

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Novel mechanism of angiotensin II-induced cardiac injury by in hypertensive rats : the critical role of ASK1 and VEGF2012

    • Author(s)
      Nako H., Yamamoto E., Kim-Mitsuyama S., et al.(10人中6番目)
    • Journal Title

      Hypertens Res

      Volume: 35(2) Pages: 194-200

    • NAID

      10030643734

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Attenuation of brain damage and cognitive impairment by direct renin inhibition in mice with chronic cerebral hypoperfusion2011

    • Author(s)
      Dong YF., Yamamoto E., Kim-Mitsuyama S., et al.(10人中6番目)
    • Journal Title

      Hypertension

      Volume: 58(4) Pages: 635-42

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Beneficial effects of combination of valsartan and amlodipine on salt-induced brain injury in hypertensive rats2011

    • Author(s)
      Dong YF., Yamamoto E., Kim-Mitsuyama S., et al.(11人中9番目)
    • Journal Title

      J Pharmacol Exp Ther

      Volume: 339(2) Pages: 358-66

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Novel mechanism of salt-induced glomerular injury : critical role of eNOS and angiotensin II2011

    • Author(s)
      Nakamura T., Yamamoto E., Kim-Mitsuyama S., et al.(11人中8番目)
    • Journal Title

      J Hypertens

      Volume: 29(8) Pages: 1528-35

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Perindopril, a centrally-active ACE inhibitor, prevents cognitive impairment in mouse models of Alzheimer's disease2011

    • Author(s)
      Dong YF., Yamamoto E, Kim-Mitsuyama S., et al.(11人中9番目)
    • Journal Title

      FASEB J

      Volume: 25(9) Pages: 2911-20

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Eplerenone potentiates protective effects of amlodipine against cardiovascular injury in salt-sensitive hypertensive rats2011

    • Author(s)
      Nakamura T., Yamamoto E., Kim-Mitsuyama S., et al.(10人中7番目)
    • Journal Title

      Hypertens Res

      Volume: 34(7) Pages: 817-24

    • NAID

      10031163263

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Pentraxin 3 is a new inflammatory marker correlated with left ventricular diastolic dysfunction and heart failure with normal ejection fraction2011

    • Author(s)
      Matsubara J., Yamamoto E., Ogawa H., et al.(15人中9番目)
    • Journal Title

      J Am Coll Cardiol

      Volume: 57(7) Pages: 861-9

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Vascular responses to 8-nitro-cyclic GMP in nondiabetic and diabetic mice2011

    • Author(s)
      Tokutomi Y, Yamamoto E, Kim-Mitsuyama S., et al.(12人中3番目)
    • Journal Title

      Br J Pharmacol

      Volume: 162(8) Pages: 1884-93

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Vascular responses to 8-nitro-cyclic GMP in non-diabetic and diabetic mice2011

    • Author(s)
      Tokutomi Y., et al
    • Journal Title

      Br J Pharmabol

      Volume: 162 Issue: 8 Pages: 1884-1893

    • DOI

      10.1111/j.1476-5381.2011.01201.x

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pentraxin 3 isa new inflammatory marker correlatedwith left ventricular diastolicdysfunction and heart failure withnormal ejection fraction2011

    • Author(s)
      Matsubara J, Sugiyama S, Nozaki T,Sugamura K, Konishi M, Ohba K, MatsuzawaY, Akiyama E, Yamamoto E, Sakamoto K,Nagayoshi Y, Kaikita K, Sumida H,Kim-Mitsuyama S, Ogawa H
    • Journal Title

      J Am CollCardiol

      Volume: 57(7) Issue: 7 Pages: 861-9

    • DOI

      10.1016/j.jacc.2010.10.018

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Eplerenone potentiates protective effects of amlodipine against cardiovascular injury in salt-sensitive hypertensive rats2011

    • Author(s)
      Nakamura T., Yamamoto E., et al
    • Journal Title

      Hypertens Res

      Volume: 34(7) Issue: 7 Pages: 817-824

    • DOI

      10.1038/hr.2011.35

    • NAID

      10031163263

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Perindopril, a centrally-active ACE inhibitor, prevents cognitive impairment in mouse models of Alzheimer's disease2011

    • Author(s)
      Dong YF., Yamamoto E., et al
    • Journal Title

      FASEB J

      Volume: 25(9) Issue: 9 Pages: 2911-2920

    • DOI

      10.1096/fj.11-182873

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Novel mechanism of salt-induced glomerular injury : critical role of eNOS and angiotensin II2011

    • Author(s)
      Nakamura T., Yamamoto E., et al
    • Journal Title

      J Hypertens

      Volume: 29(8) Issue: 8 Pages: 1528-1535

    • DOI

      10.1097/hjh.0b013e328348ca95

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Beneficial effects of combination of valsartan and amlodipine on salt-induced brain injury in hypertensive rats2011

    • Author(s)
      Dong YF., Yamamoto E., et al
    • Journal Title

      J Pharmacol Exp Ther

      Volume: 339(2) Issue: 2 Pages: 358-366

    • DOI

      10.1124/jpet.111.182576

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Attenuation of brain damage and cognitive impairment by direct renin inhibition in mice with chronic cerebral hypoperfusion2011

    • Author(s)
      Dong YF., Yamamoto E., et al
    • Journal Title

      Hypertension

      Volume: 58(4) Issue: 4 Pages: 194-200

    • DOI

      10.1161/hypertensionaha.111.173534

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Nifedipine prevents vascular endothelial dysfunction in a mouse model of obesity and type 2 diabetes, by improving eNOS dysfunction and dephosphorylation2010

    • Author(s)
      Yamamoto E., Kim-Mitsuyama S., et al.(10人中1番目)
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 403(3-4) Pages: 258-63

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Apoptosis signal-regulating kinase 1 deficiency eliminates cardiovascular injuries induced by high-salt diet2010

    • Author(s)
      Kataoka K., Yamamoto E., Kim-Mitsuyama S., et al.(9人中3番目)
    • Journal Title

      J Hypertens

      Volume: 29(1) Pages: 76-84

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Aliskiren enhances protective effects of valsartan against type 2 diabetic nephropathy in mice2010

    • Author(s)
      Dong YF., Yamamoto E., Kim-Mitsuyama S., et al.(11人中4番目)
    • Journal Title

      J Hypertens

      Volume: 28(7) Pages: 1554-65

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Benidipine, a dihydropyridine L-type/T-type calcium channel blocker, affords additive benefits for prevention of cardiorenal injury in hypertensive rats2010

    • Author(s)
      Yamamoto E., Kim-Mitsuyama S., et al.(8人中1番目)
    • Journal Title

      J Hypertens

      Volume: 28(6) Pages: 1321-9

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Benidipine, a dihydropyridine L-type/T-type calcium channel blocker, affords additive benefits for prevention of cardiorenal injury in hypertensive rats.2010

    • Author(s)
      山本英一郎
    • Journal Title

      Journal of Hypertension

      Volume: 28(6) Pages: 1321-1329

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Nifedipine prevents vascular endothelial dysfunction in a mouse model of obesity and type 2 diabetes, by improving eNOS dysfunction and dephosphorylation.2010

    • Author(s)
      山本英一郎
    • Journal Title

      Biochem Biophys Res Commun.

      Volume: 403(3-4) Pages: 258-263

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Apoptosis signal-regulating kinase 1 deficiency eliminates cardiovascular injuries induced by high-salt diet.2010

    • Author(s)
      山本英一郎
    • Journal Title

      Journal of Hypertension

      Volume: 29(1) Pages: 76-84

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] Combination of Angiotensin Receptor Blocker with Calcium Channel Blocker, than with Diuretic, Exerts More Beneficial Vascular Protective Effects2012

    • Author(s)
      山本英一郎、光山勝慶、小川久雄
    • Organizer
      第76回日本循環器学会学術集会
    • Place of Presentation
      福岡国際会議場(福岡県)
    • Year and Date
      2012-03-16
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] Direct Renin Inhibition with Aliskiren Enhances Beneficial Effects of Angiotensin II Receptor Blocker on Cardiovascular and Renal Injury in eNOS Deficient Mice2010

    • Author(s)
      山本英一郎、光山勝慶、小川久雄
    • Organizer
      第83回米国心臓協会学術集会
    • Place of Presentation
      アメリカ合衆国シカゴ市
    • Year and Date
      2010-11-17
    • Related Report
      2011 Final Research Report
  • [Presentation] Direct Renin Inhibition with Aliskiren Enhances Beneficial Effects of Angiotensin II Receptor Blocker on Cardiovascular and Renal Injury in eNOS Deficient Mice2010

    • Author(s)
      山本英一郎
    • Organizer
      第83回 米国心臓協会 学術集会
    • Place of Presentation
      (アメリカ)McCormick Place
    • Year and Date
      2010-11-17
    • Related Report
      2010 Annual Research Report
  • [Presentation] Novel Mechanism of the Beneficial Effects of Dihydropyridine Calcium Channel Blocker on Vascular Endothelial Dysfunction in Obesity and Type2 Diabetes2010

    • Author(s)
      山本英一郎、光山勝慶、小川久雄
    • Organizer
      第23回国際高血圧学会学術集会
    • Place of Presentation
      カナダバンクーバー市
    • Year and Date
      2010-09-30
    • Related Report
      2011 Final Research Report
  • [Presentation] Novel Mechanism of the Beneficial Effects of Dihydropyridine Calcium Channel Blocker on Vascular Endothelial Dysfunction in Obesity and Type2 Diabetes2010

    • Author(s)
      山本英一郎
    • Organizer
      第23回 国際高血圧学会 学術集会
    • Place of Presentation
      (カナダ)Vancduver Convention Centre
    • Year and Date
      2010-09-30
    • Related Report
      2010 Annual Research Report

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Published: 2010-08-23   Modified: 2016-04-21  

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