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Clinical and molecular biological approach to the genesis of coronary artery spasm : A study on the role of p122 protein

Research Project

Project/Area Number 20590856
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

OKUMURA Ken  Hirosaki University, 大学院・医学研究科, 教授 (20185549)

Co-Investigator(Kenkyū-buntansha) OSANAI Tomohiro  弘前大学, 大学院・医学研究科, 准教授 (00169278)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2010: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords循環器・高血圧 / 冠攣縮 / P122蛋白 / Phospholipase C / phospholipase C / Dhospholipase C
Research Abstract

A p122 protein was recently cloned to potentiate phospholipase C (PLC)-δ1 activity. To investigate the role of p122 in the enhanced vasomotility, we examined p122 expression in the cultured skin fibroblasts obtained from patients with and without coronary spasm, intracellular calcium concentration ([Ca^<2+>]_i) at baseline and after stimulation with acetylcholine in the cells transfected with p122, and promoter in genomic DNA. p122 protein and gene expression levels in patients with coronary spasm (n=11) were enhanced compared with that in control subjects (n=9) (both p<0.01). [Ca^<2+>]_i at baseline and the peak increase in [Ca^<2+>]_i in response to acetylcholine were both two times higher in cells transfected with p122 than in those without p122. In the p122 promoter analysis, the -228G/A and -1466C/T variants revealed the increase in luciferase activitiy. The -228G/A variant was more frequent in male patients than in male controls (p<0.05). In conclusions, p122 is upregulated in patients with coronary spasm, which causes increased [Ca^<2+>]_i to acetylcholine and thereby seems to be related to enhanced coronary vasomotility

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (51 results)

All 2011 2010 2009 2008 Other

All Journal Article (36 results) (of which Peer Reviewed: 27 results) Presentation (7 results) Book (7 results) Remarks (1 results)

  • [Journal Article] Effects of pravastatin and rosuvastatin on the generation of adiponectin in the visceral adipose tissue in patients with coronary artery disease.2011

    • Author(s)
      Yokoyama H, Osanai T, Okumura K, et al
    • Journal Title

      Fundam Clin Pharmacol. 25

      Pages: 378-387

    • Related Report
      2010 Final Research Report
  • [Journal Article] Effects of pravastatin and rosuvastatin on the generation of adiponectin in the visceral adipose tissue in patients with coronary artery disease.2011

    • Author(s)
      Yokoyama H, Okumura K, et al.
    • Journal Title

      Fundam Clin Pharmacol

      Volume: 25 Pages: 378-387

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Novel pro-atherogenic molecule coupling factor 6 is elevated in patients with stroke : a possible linkage to homocysteine.2010

    • Author(s)
      Osanai T, Okumura K, et al
    • Journal Title

      Ann Med. 42

      Pages: 79-86

    • Related Report
      2010 Final Research Report
  • [Journal Article] p122 Protein Enhances Intracellular Calcium Increase to Acetylcholine. Its Possible Role in the Pathogenesis of Coronary Spastic Angina.2010

    • Author(s)
      Murakami R, Osanai T, Okumura K, et al
    • Journal Title

      Arterioscler Thromb Vasc Biol. 30

      Pages: 1968-1975

    • Related Report
      2010 Final Research Report
  • [Journal Article] Effects of telmisartan on markers of ventricular remodeling in patients with acute myocardial infarction : comparison with enalapril.2010

    • Author(s)
      Yokota T, Osanai T, Okumura K, et al
    • Journal Title

      Heart Vessels. 25

      Pages: 460-8

    • Related Report
      2010 Final Research Report
  • [Journal Article] Effects of telmisartan on markers of ventricular remodeling in patients with acute myocardial infarction : comparison with enalapril.2010

    • Author(s)
      Yokota T, Okumura K, et al
    • Journal Title

      Heart Vessels

      Volume: 25 Pages: 460-468

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] pl22 Protein Enhances Intracellular Calcium Increase to Acetylcholine . Its Possible Role in the Pathogenesis of Coronary Spastic Angina.2010

    • Author(s)
      Murakami R, Okumura K, et al
    • Journal Title

      Thromb Vase Biol

      Volume: 30 Pages: 1968-1975

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Novel pro-atherogenic molecule-coupling factor 6 is elevated in patients with stroke : a possible linkage to homocysteine.2010

    • Author(s)
      Osanai T, Okumura K, et al
    • Journal Title

      Ann Med

      Volume: 42 Pages: 79-86

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Comparison of the effects of long-acting nifedipine CR and diltiazem R in patients with vasospastic angina : Aomori coronary spastic angina study.2010

    • Author(s)
      Higuma T, Okumura K, et al
    • Journal Title

      J Cardiol

      Volume: 56 Pages: 354-360

    • NAID

      10028189779

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Overexpression of coupling factor 6 causes cardiac dysfunction under high salt diet in mice.2010

    • Author(s)
      Ashitate T, Okumura K, et al
    • Journal Title

      J Hypertens

      Volume: 28 Pages: 2243-2251

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Brain natriuretic peptide is released from human astrocytoma cell line U373MG under hypoxia : A possible role in anti-apoptosis.2010

    • Author(s)
      Katoh C, Okumura K, et al
    • Journal Title

      J Endocrinol

      Volume: 208 Pages: 51-57

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Coupling factor 6 enhances Src-mediated responsiveness to angiotensin II in resistance arterioles and cells.2009

    • Author(s)
      Osanai T, Okumura K, et al
    • Journal Title

      Cardiovasc Res 81

      Pages: 780-787

    • Related Report
      2010 Final Research Report 2009 Annual Research Report
  • [Journal Article] Upregulation of soluble vascular endothelial growth factor receptor type 1 by endogenous prostacyclin inhibitor coupling factor 6 in vascular endothelial cells : a role of acidosis-induced c-Src activation.2009

    • Author(s)
      Echizen T, Osanai T, Okumura K, et al
    • Journal Title

      Hypertens Res. 32

      Pages: 182-187

    • NAID

      10024829936

    • Related Report
      2010 Final Research Report
  • [Journal Article] Effect of pilsicainide on dominant frequency in the right and left atria and pulmonary veins during atrial fibrillation : Association with its atrial fibrillation terminating effect.2009

    • Author(s)
      Horiuchi D, Okumura K, et al
    • Journal Title

      Eur J Pharmacol 608

      Pages: 54-61

    • Related Report
      2010 Final Research Report
  • [Journal Article] Impact of telmisartan on coronary stenting in patients with acute myocardial infarction compared with enalapril.2009

    • Author(s)
      Yokoyama J, Osanai T, Okumura K, et al
    • Journal Title

      Int J Cardiol 132

      Pages: 114-120

    • Related Report
      2010 Final Research Report
  • [Journal Article] Coupling factor 6 as a novel vasoactive and proatherogenic peptide in vascular endothelial cells.2009

    • Author(s)
      Osanai T, Magota K, Okumura K
    • Journal Title

      Naunyn-Schmied Arch Pharmacol 380

      Pages: 205-214

    • Related Report
      2010 Final Research Report
  • [Journal Article] Impact of telmisartan on coronary stenting in patients with acute myocardial infarction compared with enalapril.2009

    • Author(s)
      Yokoyama J, Okumura K, et al
    • Journal Title

      Int J Cardiol 132

      Pages: 114-120

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effect of pilsicainide on dominant frequency in the right and left atria and pulmonary veins during atrial fibrillation : Association with its atrial fibrillation terminating effect2009

    • Author(s)
      Horiuchi D, Iwasa A, et al
    • Journal Title

      Eur J Pharmacol 608

      Pages: 54-61

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Upregulation of soluble vascular endothelial growth factor receptor type 1 by endogenous prostacyclin inhibitor coupling factor 6 in vascular endothelial cells : a role of acidosis-induced c-Src activation.2009

    • Author(s)
      Echizen T, Okumura K, et al
    • Journal Title

      Hypertens Res. 32

      Pages: 182-187

    • NAID

      10024829936

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Generation and characterization of coupling factor 6-oberexpressing transgenic mice.2009

    • Author(s)
      Ashitate T, Okumura K, et al
    • Journal Title

      Hirosaki Med J 60

      Pages: 18-26

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Upregulation of insulin-like growth factor-1 gene expression in cardiac myocytes by hypoxia : mechanism for its cardioprotective effect.2009

    • Author(s)
      Katoh C, Okumura K, et al
    • Journal Title

      Hirosaki Med J 60

      Pages: 36-44

    • NAID

      110007079178

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Amiodarone Attenuates the Upregulated Matrix Metalloproteinase-2 Activity in a Rat Myocardial Infarction Model.2009

    • Author(s)
      Horiuchi D, Okumura K, et al
    • Journal Title

      Hirosaki Med J 60

      Pages: 45-53

    • NAID

      110007079179

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Impairment of calcium-activated potassium channels in endothelium-derived hyperpolarizing factor responses in spontaneously hypertensive rats.2009

    • Author(s)
      Hasegawa K, Okumura K, et al
    • Journal Title

      Hirosaki Med J 60

      Pages: 86-95

    • NAID

      110007079182

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Coupling factor 6 as a novel vasoactive and proatherogenic peptide in vascular endothelial cells.2009

    • Author(s)
      Osanai T, Okumura K, et al
    • Journal Title

      Naunyn-Schmied Arch Pharmacol 380

      Pages: 205-214

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] From 4-links to 5-links of "Chain of survival"--Post-resus citation care is critical for good neurological recovery--2009

    • Author(s)
      Hanada H, Okumura K, et al
    • Journal Title

      Circ J 73

      Pages: 1797-1798

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Coupling factor 6 enhances Src-mediated responsiveness to angiotensin II in resistance arterioles and cells2009

    • Author(s)
      Ken Okumura, et.al.
    • Journal Title

      Cardiovasc Res 81

      Pages: 780-787

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effect of pilsicaihide on dominant frequency in the right and left atria and pulmonary veins during atrial fibrillation : Association with its atrial fibrillation terminating effect2009

    • Author(s)
      Ken Okumura, et.al.
    • Journal Title

      Eur J Pharmacol 608

      Pages: 54-61

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Upregulation of soluble vascular endothelial growth factor receptor type 1 by endogenous prostacyclin inhibitor coupling factor 6 in vascular endothelial cells : a role of acidosis-induced c-Src activation2009

    • Author(s)
      Ken Okumura, et.al.
    • Journal Title

      Hypertens Res 32

      Pages: 182-187

    • NAID

      10024829936

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Generation and characterization of coupling factor 6-overexpressing transgenic mice2009

    • Author(s)
      Ken Okumura, et.al.
    • Journal Title

      Hirosaki Medical Journal 60

      Pages: 18-26

    • NAID

      110007079176

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Upregulation of insulin-like growth factor-1 gene expression in cardiac myocytes by hypoxia : mechanism for its cardionrotective effect2009

    • Author(s)
      Ken Okumura, et.al.
    • Journal Title

      Hirosaki Medical Journal 60

      Pages: 36-44

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Impairment of calcium-activated potassium channels in endothelium-derived hyperpolarizing factor responses in spontaneously hypertensive rats2009

    • Author(s)
      Ken Okumura, et.al.
    • Journal Title

      Hirosaki Medical Journal 60

      Pages: 86-95

    • NAID

      110007079182

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Increased Adiponectin synthesis in the visceral adipose tissue in men with coronary artery disease treated with pravastatin : A role of the attenuation of oxidative stress2008

    • Author(s)
      Ken Okumura, et.al.
    • Journal Title

      Atherosclerosis 199

      Pages: 378-383

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Vasoconstrictor effect of aldosterone via angiotensin II type 1(AT_1) receptor : possible role of AT_1 receptor dimerization2008

    • Author(s)
      Ken Okumura, et.al.
    • Journal Title

      Cardiovasc Res 79

      Pages: 169-178

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Decreased plasma and cardiac matrix metalloproteinase activities in patients with coronary artery disease and treated with pravastatin2008

    • Author(s)
      Ken Okumura, et.al.
    • Journal Title

      European J Pharmacol 594

      Pages: 146-151

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Coupling factor 6 downregulates platelet endothelial cell adhesion molecule-1 via c-Src activation and acts as a proatherogenic molecule2008

    • Author(s)
      Ken Okumura, et.al.
    • Journal Title

      Atherosclerosis 200

      Pages: 45-50

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Elevated plasma, brain natriuretic peptide levels independent of heart disease in acute ischemic stroke : Correlation with stroke severity2008

    • Author(s)
      Ken Okumura, et.al.
    • Journal Title

      Hypertens Res 31

      Pages: 1695-1702

    • NAID

      10024362177

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] Coronary Vasospasm Induced In Transgenic Mice With Variant Phospholipase C-δ1(R257H).2010

    • Author(s)
      Shibutani S, Okumura K, et al
    • Organizer
      アメリカ心臓病学会(AHA)
    • Place of Presentation
      フロリダ
    • Year and Date
      2010-11-15
    • Related Report
      2010 Final Research Report
  • [Presentation] Coronary Vasospasm Induced In Transgenic Mice With Variant Phospholipase C-δ1(R257H)2010

    • Author(s)
      Shibutani S, Ken Okumura, et al
    • Organizer
      第74回アメリカ心臓病学会
    • Place of Presentation
      Orange County Convention Center Orlando, Fla.
    • Year and Date
      2010-11-15
    • Related Report
      2010 Annual Research Report
  • [Presentation] 頻発する心室性期外収縮へのアプローチ2010

    • Author(s)
      奥村謙
    • Organizer
      第74回日本循環器学会総会・学術集会
    • Place of Presentation
      国立京都国際会館
    • Year and Date
      2010-03-07
    • Related Report
      2009 Annual Research Report
  • [Presentation] カテーテルアブレーションの進歩-3次元マッピングの有用性について2009

    • Author(s)
      奥村謙
    • Organizer
      第107回日本循環器学会九州地方会
    • Place of Presentation
      宮崎県農協会館
    • Year and Date
      2009-12-05
    • Related Report
      2009 Annual Research Report
  • [Presentation] Management of Atrial Fibrillation : Medical or Ablation2009

    • Author(s)
      奥村謙
    • Organizer
      第57回日本心臓病学会学術集会(第12回JCC-ACCジョイントシンポジウム)
    • Place of Presentation
      ロイトン札幌
    • Year and Date
      2009-09-20
    • Related Report
      2009 Annual Research Report
  • [Presentation] P122 Protein a positive regulator for phospholipase C-δ1, is upregulated and involved in enhanced calcium signaling in human coronary spasm.2008

    • Author(s)
      Okumura K, et al
    • Organizer
      アメリカ心臓病学会(AHA)
    • Place of Presentation
      ニューオリンズ
    • Year and Date
      2008-11-10
    • Related Report
      2010 Final Research Report
  • [Presentation] P122 protein, a positive regulator for phospholipase C-δ1, is upregulated and involved in enhanced calcium signaling in human coronary spasm2008

    • Author(s)
      Ken Okumura, et.al.
    • Organizer
      2008年米国心臓病学会(AHA)
    • Place of Presentation
      米国ニューオリンズ
    • Year and Date
      2008-11-10
    • Related Report
      2008 Annual Research Report
  • [Book] 心房細動の治療と管理Q&A第2版2009

    • Author(s)
      奥村謙
    • Total Pages
      3
    • Related Report
      2010 Final Research Report
  • [Book] 頻拍発症機序の解析法(新・心臓病プラクティス13)2009

    • Author(s)
      奥村謙
    • Related Report
      2010 Final Research Report
  • [Book] 心臓リズムマネージメントを究める2009

    • Author(s)
      奥村謙
    • Publisher
      メジカルビュー社
    • Related Report
      2010 Final Research Report
  • [Book] 頻拍発症機序の解析法新・心臓病プラクティス132009

    • Author(s)
      奥村謙, 他
    • Total Pages
      519
    • Publisher
      文光堂
    • Related Report
      2009 Annual Research Report
  • [Book] 心房細動の治療と管理Q&A第2版2009

    • Author(s)
      奥村謙, 他
    • Total Pages
      306
    • Publisher
      医学書院
    • Related Report
      2009 Annual Research Report
  • [Book] 心臓リズムマネージメントを究める2009

    • Author(s)
      奥村謙, 他
    • Total Pages
      473
    • Publisher
      メジカルビュー社
    • Related Report
      2009 Annual Research Report
  • [Book] 心房細動の治療と管理Q&A第2版2009

    • Author(s)
      奥村謙
    • Total Pages
      306
    • Publisher
      医学書院
    • Related Report
      2008 Annual Research Report
  • [Remarks] ホームページ等

    • Related Report
      2010 Final Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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