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Antiatherosclerotic therapy using cell differentiation-promoting effect of biologically active peptides

Research Project

Project/Area Number 18590829
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionNational Cardiovascular Center Research Institute

Principal Investigator

HORIO Takeshi  National Cardiovascular Center Research Institute, Division of Hypertension and Nephrology, Department of Medicine, Medical doctor (50393228)

Co-Investigator(Kenkyū-buntansha) TOKUDOME Takeshi  National Cardiovascular Center Research Institute, Department of Etiology and Pathogenesis, Laboratory chief (00443474)
KISHIMOTO Ichiro  Division of Atherosclerosis and Diabetes, Department of medicine, Medical doctor (80312221)
KANGAWA Kenji  Research Institute, Director (00112417)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,890,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥390,000)
Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2006: ¥2,200,000 (Direct Cost: ¥2,200,000)
KeywordsAtherosclerosis / Natriuretic peptides / Neovascularization / 平滑筋細胞
Research Abstract

We first examined the expression of receptors for natriuretic peptides(ANP, BNP, CNP) in wire-injured femoral arteries in mice. Significant expressions of both GC-A(receptor for ANP and BNP) and GC-B(receptor for CNP) were found in neointima after 3 weeks of wire injury, and the expression level of GC-A was higher than that of GC-B. When the extent of wire injury-induced neointima formation was compared between wild-type and GC-A knockout mice, the area of neointima was greater in GC-A knockout mice. This result suggested the possibility that endogenous ANP and BNP released from the heart inhibited atherosclerotic change of femoral artery after wire injury. To further examine the role of endogenous ANP and BNP in neovascularization observed in atherosclerotic lesions, lower limb-ischemic model was made in both wild-type and GC-A knockout mice, and the recovery of blood flow was evaluated. The blood flow was restored to about 70% after 3 weeks in wild-type mice. On the other hand, inter … More estingly, the recovery rate of blood flow in GC-A knockout mice was about 20%, and approximately half of them had necrotized lower limbs. The finding suggested that endogenous ANP and BNP might play an important role in the angiogenesis in ischemic lesions. From these results, an in vitro study was designed to investigate whether ANP and BNP, stimulate cyclic GMP(cGMP) accumulation in vascular endothelial progenitor cells derived from human blood mononuclear cells. As a result, intracellular cGMP levels were remarkably elevated after stimulation with ANP and BNP, suggesting that these peptides have a direct effect on endothelial progenitor cells. Our findings indicate that endogenous ANP and BNP are involved not only in the inhibition of the formation of atherosclerotic lesions, but also in the promotion of neovascularization in those lesions. Thus, the present study provided a great progress forclinical application of antiatherosclerotic therapy using cell differentiation-promoting effect of ANP and BNP. We will forward further investigations about antiatherosclerotic effects and therapeutic application of CNP, adrenomedulin, and ghrelin. Less

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (50 results)

All 2008 2007 2006 Other

All Journal Article (33 results) (of which Peer Reviewed: 9 results) Presentation (15 results) Book (2 results)

  • [Journal Article] Exogenous ghrelin attenuates the progression of chronic hypoxia-induced pulmonary hypertension in conscious rats2008

    • Author(s)
      Daryl O.Schwenke, et. al.
    • Journal Title

      Endocrinology 149

      Pages: 237-44

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Ghrelin suppresses cardiac sympathetic activity and prevents early left ventricular remodeling in rats with myocardial infarction2008

    • Author(s)
      Takeshi Soeki, et. al.
    • Journal Title

      American Journal of Physiology 294

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Plasma adrenomedullin as an independent predictor of future cardiovascular events in high-risk patients: comparison with C-reactive protein and adiponectin2008

    • Author(s)
      Hidenori Nishida, et. al.
    • Journal Title

      Peptides 29

      Pages: 599-605

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] 高血圧性心不全-病態と診断・治療の現状 高血圧性心不全とナトリウム利尿ホルモン2008

    • Author(s)
      堀尾武史
    • Journal Title

      血圧 15

      Pages: 161-4

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Exogenous ghrelin attenuates the progression of chronic hypoxic-induced pulmonary hypertension in conscious rats.2008

    • Author(s)
      Daryl O. Schwenke, et. al.
    • Journal Title

      Endocrinology 149

      Pages: 237-44

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Ghrelin suppresses cardiac sympathetic activity and prevents early left ventricular remodeling in rats with myocardial infarction.2008

    • Author(s)
      Takeshi Soeki, et. al.
    • Journal Title

      Am J physiol 294

      Pages: 426-32

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Plasma adrenomedullin as an independent predictor of future cardiovascular events in high-risk patients : comparison of C-reactive protein and adiponectin.2008

    • Author(s)
      Hidenori Nishida, et. al.
    • Journal Title

      Peptides 29

      Pages: 599-605

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Hypertensive heart failure and natriuretic peptides.2008

    • Author(s)
      Takeshi Horio, et. al.
    • Journal Title

      J Blood Press 15

      Pages: 161-4

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Ghrelin suppresses cardiac sympathetic activity and prevents early left ventricular remodeling in rats with myocardial infarction2008

    • Author(s)
      Takeshi Soeki, et. al.
    • Journal Title

      Am J Physiol Heart Circ Physiol 294

      Pages: 426-432

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Plasma adrenomedullin as an independent predictor of future cardiovascular events in high-risk patients2008

    • Author(s)
      Hidenori Nishida, et. al.
    • Journal Title

      Peptides 29

      Pages: 599-605

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 高血圧性心不全とナトリウム利尿ホルモン2008

    • Author(s)
      堀尾 武史
    • Journal Title

      血圧 15

      Pages: 161-164

    • Related Report
      2007 Annual Research Report
  • [Journal Article] Midregional proadrenomedullin reflects cardiac dysfunction in hemodialysis patients with cardiovascular disease2007

    • Author(s)
      Fumiki Yoshihara, et. al.
    • Journal Title

      Nephrology, Dialysis, and Transplantation 22

      Pages: 2263-8

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] 心不全(上)成因・病態に関する基礎的研究 ナトリウム利尿ペプチド2007

    • Author(s)
      徳留 健, 他
    • Journal Title

      日本臨床 65(増刊号4)

      Pages: 165-9

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] 内因性ナトリウム利尿ペプチドの心保護作用-遺伝子改変マウスからのレッスン2007

    • Author(s)
      徳留 健, 他
    • Journal Title

      循環器病研究の進歩 28

      Pages: 40-52

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Midregional proadrenomedullin reflects cardiac dysfunction in hemodialysis patients with cardiovascular disease.2007

    • Author(s)
      Fumiki Yoshihara, et. al.
    • Journal Title

      Nephrol Dial Transplant 22

      Pages: 2263-8

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Cardioprotective effect of endogenous natriuretic peptides. Lesson from gene-targeting mice.2007

    • Author(s)
      Takeshi Tokudome, et. al.
    • Journal Title

      Advance in Cardiovasc Dis 28

      Pages: 40-52

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Midregional proadrenomedullin reflects cardiac dysfunction in hemodialysis patients with cardiovascular disease2007

    • Author(s)
      Fumiki Yoshihara, et al.
    • Journal Title

      Nephrology, Dialysis, and Transplantation 22(in press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Adiponectin and inflammatory markers in peripheral arterial occlusive disease2006

    • Author(s)
      Yoshio Iwashima, et. al.
    • Journal Title

      Atherosclerosis 188

      Pages: 384-90

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Adiponectin and renal function,and implication as a risk of cardiovascular disease2006

    • Author(s)
      Yoshio Iwashima, et. al.
    • Journal Title

      American Journal of Cardiology 98

      Pages: 1603-8

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] 慢性心不全治療の進歩-成因と臨床研究-心不全の発症進展機序 サイトカイン2006

    • Author(s)
      堀尾武史
    • Journal Title

      日本臨床 64

      Pages: 843-7

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] 高血圧(下巻)-最新の研究動向- 臓器障害の進展予測検査 MMP/TIMP比2006

    • Author(s)
      堀尾武史, 他
    • Journal Title

      日本臨床 64(増刊号6)

      Pages: 171-5

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Adiponectin and inflammatory markers in peripheral arterial occlusive disease.2006

    • Author(s)
      Yoshio Iwashima, et. al.
    • Journal Title

      Atherosclerosis 188

      Pages: 384-90

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Progress in therapy of chronic heart failure. Involvement of cytokines in the initiation and development of heart failure.2006

    • Author(s)
      Takeshi Horio
    • Journal Title

      Nihon Rinsho 64

      Pages: 843-7

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Evaluation of target organ damage in hypertension. MMP/TIMP ratio.2006

    • Author(s)
      Takeshi Horio, et. al.
    • Journal Title

      Nihon Rinsho 64(Suppl 6)

      Pages: 171-5

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Natriuretic peptides in the Peptides cardiovascular system.2006

    • Author(s)
      Kastin AJ, ed ; Naoto Minamino, et. al.
    • Journal Title

      Handbook of Biologically Active Academic Press

      Pages: 1199-1207

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Adiponectin and inflammatory markers in peripheral arterial occlusive disease2006

    • Author(s)
      Yoshio Iwashima, et al.
    • Journal Title

      Atherosclerosis 188・2

      Pages: 384-90

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Adiponectin and renal function, and implication as a risk of cardiovascular disease2006

    • Author(s)
      Yoshio Iwashima, et al.
    • Journal Title

      American Journal of Cardiology 98・12

      Pages: 1603-8

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 心不全の発症進展機序 サイトカイン2006

    • Author(s)
      堀尾 武史
    • Journal Title

      日本臨床 64(5)

      Pages: 843-7

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 臓器障害の進展予測検査 MMP/TIMP比2006

    • Author(s)
      堀尾 武史 ら
    • Journal Title

      日本臨床 64(増刊号6)

      Pages: 171-5

    • Related Report
      2006 Annual Research Report
  • [Journal Article] RGS4 mediates anti-hypertrophic effects of locally secreted natriuretic peptides in the heart

    • Author(s)
      Takeshi Tokudome, et. al.
    • Journal Title

      Circulation (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Adiponectin and renal function, and implication as a risk of cardiovascular disease.

    • Author(s)
      Yoshio Iwashima, et. al.
    • Journal Title

      Am J Cardiol 98

      Pages: 1603-8

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Basic research for pathophysiology of heart failure. 2007 Natriuretic peptides.

    • Author(s)
      Takeshi Tokudome, et. al.
    • Journal Title

      Nihon Rinsho 65(Suppl 4)

      Pages: 165-9

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] RGS4 mediates anti-hypertrophic effects of locally secreted natriuretic peptides in the heart.

    • Author(s)
      Takeshi Tokudome, et. al.
    • Journal Title

      Circulation (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] C型ナトリウム利尿ペプチド(CNP):心臓における役割2008

    • Author(s)
      堀尾 武史
    • Organizer
      第37回日本心脈管作動物質学会(シンポジウム)
    • Place of Presentation
      仙台国際センター
    • Year and Date
      2008-02-02
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Role of C-type natriuretic peptide in the heart.2008

    • Author(s)
      Takeshi Hono, et. al.
    • Organizer
      37th Scientific Session of the Japanese Society of Circulation Research
    • Place of Presentation
      Sendai
    • Year and Date
      2008-02-02
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] C型ナトリウム利尿ペプチド(CNP) : 心臓における役割2008

    • Author(s)
      堀尾 武史
    • Organizer
      第37回日本心脈管作動物質学会(シンポジウム)
    • Place of Presentation
      仙台(仙台国際センター)
    • Year and Date
      2008-02-02
    • Related Report
      2007 Annual Research Report
  • [Presentation] Plasma adrenomedullin as an independent predictor of future cardiovascular events in hypertensive patients2007

    • Author(s)
      Hidenori Nishida, et. al.
    • Organizer
      61st Annual High Blood Pressure Research Conference
    • Place of Presentation
      米国アリゾナ州 ツーソン
    • Year and Date
      2007-09-28
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Plasma adrenomedullin as an independent predictor of future cardiovascular events in hypertensive patients.2007

    • Author(s)
      Hidenori Nishida, et. al.
    • Organizer
      61st Annual High Blood Pressure Research Conference
    • Place of Presentation
      Tucson
    • Year and Date
      2007-09-28
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Regulator of G-protein signaling 4 mediates antihypertrophic effect of endogenous natriuretic peptides in the heart2007

    • Author(s)
      徳留 健, 他
    • Organizer
      第11回日本心不全学会学術集会
    • Place of Presentation
      ヒルトン東京ベイ
    • Year and Date
      2007-09-09
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Regulator of G-protein signaling 4 mediates antihypertrophic effect of endogenous natriuretic peptides in the heart.2007

    • Author(s)
      Takeshi Tokudome, et. al.
    • Organizer
      11th Annual Scientific Meeting of the Japanese Heart Failure Society
    • Place of Presentation
      Chiba
    • Year and Date
      2007-09-09
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Adrenomedullin as an independent predictor of future Japanese caidiovascular events in patients with cardiovascular risk factors.2007

    • Author(s)
      Hidenori Nishida, et. al.
    • Organizer
      71st Annual Scientific Meeting of the Circulation Society
    • Place of Presentation
      Kobe
    • Year and Date
      2007-07-17
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Plasma adrenomedullin and atherosclerotic disease:usefulness as a predictor of future cardiovascular events2007

    • Author(s)
      堀尾 武史, 他
    • Organizer
      第39回日本動脈硬化学会総会(シンポジウム)
    • Place of Presentation
      大阪国際会議場
    • Year and Date
      2007-07-14
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Plasma adrenomedullin and atherosclerotic disease : usefulness as a predictor of future cardiovascular events.2007

    • Author(s)
      Takeshi Horio
    • Organizer
      39th Annual Scientific Meeting of the Japanese Atherosclerotic Society
    • Place of Presentation
      Osaka
    • Year and Date
      2007-07-14
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Regulator of G-protein signaling-4 mediates antihypertrophic effect of atrial natriuretic peptide in cardiac myocytes2007

    • Author(s)
      徳留 健, 他
    • Organizer
      第71回日本循環器学会総会・学術集会
    • Place of Presentation
      神戸国際会議場
    • Year and Date
      2007-03-17
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Adrenomedullin as an independent predictor of future cardiovascular events in patients with cardiovascular risk factors2007

    • Author(s)
      西田 秀範, 他
    • Organizer
      第71回日本循環器学会総会・学術集会
    • Place of Presentation
      神戸国際会議場
    • Year and Date
      2007-03-17
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Regulator of G-protein signaling-4 mediates antihypertrophic effect of atrial natriuretic peptide in cardiac myocytes.2007

    • Author(s)
      Takeshi Tokudome, et. al.
    • Organizer
      71st Annual Scientific Meeting of the Japanese Circulation Society
    • Place of Presentation
      Kobe
    • Year and Date
      2007-03-17
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 内因性ANP、BNPの心臓リモデリング抑制効果のメカニズム2006

    • Author(s)
      徳留 健, 他
    • Organizer
      第10回日本心血管内分泌代謝学会学術総会
    • Place of Presentation
      福井フェニックスプラザ
    • Year and Date
      2006-11-17
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Mechanism of inhibition by endogenous ANP and BNP of cardiac remodeling.2006

    • Author(s)
      Takeshi Tokudome, et. al.
    • Organizer
      10th Scientific Session of the Society of Cardiovascular Endocrinology and Merabolism
    • Place of Presentation
      Fukui
    • Year and Date
      2006-11-17
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] Handbook of biologically active peptides:Natriuretic peptides in the cardiovascular2006

    • Author(s)
      Naoto Minamino, et. al.
    • Publisher
      Elsevier,Burlington,MA,USA
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] Handbook of Biologically Active Peptides2006

    • Author(s)
      Naoto Minamino, et al.
    • Total Pages
      1595
    • Publisher
      Elsevier, Burlington, MA, USA
    • Related Report
      2006 Annual Research Report

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Published: 2006-04-01   Modified: 2016-04-21  

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