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Molecular mechanisms of advanced atherosclerosis in chronic renal failure

Research Project

Project/Area Number 19590828
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

UEMURA Shiro  Nara Medical University, 医学部, 講師 (80232792)

Co-Investigator(Kenkyū-buntansha) SAITO Yoshihiko  奈良県立医科大学, 医学部, 教授 (30250260)
Project Period (FY) 2007 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords腎不全 / 再生医学 / 心血管
Research Abstract

慢性腎臓病(CKD)は心血管病(CVD)の独立した危険因子であるが、CVDの発症に係わる分子機序は明らかではなかった。本研究では動脈硬化進展作用を有する胎盤成長因子(PlGF)およびその内因性阻害因子である可溶性Fms-like tyrosine kinase 1; 可溶性FLT-1)に着目し、CKD患者における可溶性FLT-1関連分子の動態および動脈硬化病変の進展に寄与するメカニズムの解析を行なった。その結果, CKDの進展に伴う腎での可溶性FLT-1産生低下および血中可溶性FLT-1濃度の低下が, CKD患者における冠動脈病変の重症度を規定する重要な因子であることが判明した. さらにCKD合併動脈硬化マウスモデルを用いた実験により, リコンビナント可溶性FLT-1蛋白の持続投与が動脈硬化病変の進展を抑制することを明らかにし, 可溶性FLT-1が新しい創薬標的分子になる可能性を示した.

Report

(3 results)
  • 2008 Annual Research Report   Final Research Report ( PDF )
  • 2007 Annual Research Report
  • Research Products

    (32 results)

All 2009 2008 2007 Other

All Journal Article (18 results) (of which Peer Reviewed: 18 results) Presentation (8 results) Book (4 results) Remarks (2 results)

  • [Journal Article] Treatment with Recombinant Placental Growth Factor (PlGF) Enhances both Angiogenesis and Arteriogenesis and Improves Survival after Myocardial Infarction2009

    • Author(s)
      Takeda Y, Uemura S, Saito Y, (and15 authors)
    • Journal Title

      PLGF therapy in acute myocardial infarction. Circ J (in press)

    • NAID

      10025934995

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Novel application of black-blood echo-planar imaging to the assessment of myocardial infarction2009

    • Author(s)
      Okayama S, Uemura S, Saito Y, (and 6 authors)
    • Journal Title

      Heart and Vessels (in press)

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of aldosterone and cortisol production by the transcriptional repressor neuron restrictive silencer factor2009

    • Author(s)
      Somekawa S, UemuraS, Saito Y, (and 10 authors)
    • Journal Title

      Endocrinology (in press)

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] authors). Low-dose aspirin for primary prevention of atherosclerotic events in patients with type 2 diabetes : a randomized controlled trial2008

    • Author(s)
      Ogawa H, Uemura S, Saito Y, (and 6 authors)
    • Journal Title

      JAMA 300

      Pages: 1742-1747

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Effects of a 3-hydroxy3-methylglutaryl coenzyme A reductase inhibitor, fluvastatin, on coronary spasm after withdrawal of calciumchannel blockers2008

    • Author(s)
      Yasue H, Uemura S, Saito Y, (and 15 authors)
    • Journal Title

      J Am Coll Cardiol 51(18)

      Pages: 1742-8

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Acute myocardial infarction as a systemic prothrombotic condition evidenced by increased von Willebrand factor protein over ADAMTS13 activity in coronary and systemic circulation2008

    • Author(s)
      Horii M, Uemura S, Saito Y, (and 9 authors)
    • Journal Title

      Heart Vessel 23(5)

      Pages: 301-307

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] The specific mineralocorticoid receptor blocker eplerenone attenuates left ventricular remodeling in mice lacking the gene encoding guanylyl cyclase-A2008

    • Author(s)
      Zhang Q, Saito Y, Uemura S, (and 7 authors)
    • Journal Title

      Hypertens Res 31(6)

      Pages: 1251-6

    • NAID

      10021936878

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Progression of non-culprit coronary artery atherosclerosis after acute myocardial infarction in comparison with stable angina pectoris2008

    • Author(s)
      Okayama S, Uemura S, Saito Y, (and 13 authors)
    • Journal Title

      J Atheroscler Thromb (in press)

    • NAID

      10024363253

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Low-dose aspirin for primary prevention of atherosclerotic events in patients with type 2 diabetes : a randomized controlled trial.2008

    • Author(s)
      Ogawa H, Uemura S, Saito Y, et al
    • Journal Title

      JAMA 300

      Pages: 2134-2141

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, fluvastatin, on coronary spasm after withdrawal of calcium-channel blockers.2008

    • Author(s)
      Yasue H, Uemura S, Saito Y, et al
    • Journal Title

      JACC 51

      Pages: 1742-1748

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Acute myocardial infarction as a systemic prothrombotic condition evidenced by increased von Willebrand factor protein over ADAMTS13 activity in coronary and systemic circulation.2008

    • Author(s)
      Horii M, Uemura S, Saito Y, et al
    • Journal Title

      Heart Vessel 23

      Pages: 301-307

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Detection of infarct-related myocardial edema using cardiac diffusion-weighted magnetic resonance imaging2007

    • Author(s)
      Okayama S, Uemura S, Saito Y.
    • Journal Title

      Int J Cardiol 123(1)

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Ultrasound accelerates thrombolysis of acutely induced platelet-rich thrombi similar to those in acute myocardial infarction2007

    • Author(s)
      Kawata H, Uemura S, Saito Y, (and 8 authors)
    • Journal Title

      Circ J 71(10)

      Pages: 1643-8

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Intracoronary trans plantation of nonexpanded peripheral blood-derived mononuclear cells promotes improvement of cardiac function in patients with acute myocardial infarction2007

    • Author(s)
      Tatsumi T Uemura S, Saito Y, (and 21 authors)
    • Journal Title

      Circ J 71(8)

      Pages: 1199-207

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] ANP is cleared much faster than BNP in patients with congestive heart failure2007

    • Author(s)
      Kimura K, Uemura S, Saito Y, (and 4 authors)
    • Journal Title

      Eur J Clin Phar 63(7)

      Pages: 699-70

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] ANP is cleared much faster than BNP in patients with congestive heart failure2007

    • Author(s)
      Kimura K, et. Al
    • Journal Title

      Eur J Clin Pharmacol 63

      Pages: 699-702

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ultrasound accelerates thrombolysis of acutely induced platelet-rich thrombus similar to those in acute myocardial infarction2007

    • Author(s)
      Kawate H, et. Al
    • Journal Title

      Circ J 71

      Pages: 1643-1648

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Continuing improvement of cardiac sympathetic activity on I-123 MIBG scintigraphy in a patient with hypertrophic obstructive cardiomyopathy after percutaneous transluminal septal myocardial ablation

    • Author(s)
      Okayama S, Uemura S, Saito Y, (and 2 authors)
    • Journal Title

      J Nucl Cardiol 15(5)

      Pages: 31-34

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Presentation] Soluble Flt-1 is a novel biomarker for the development of severe atherosclerosis in renal dysfunction2009

    • Author(s)
      Saito Y, Uemura S, et al
    • Organizer
      The 73^<rd> Annual Scientific Meeting of the Japanese Circulation Society
    • Place of Presentation
      大阪
    • Year and Date
      2009-03-20
    • Related Report
      2008 Annual Research Report
  • [Presentation] Soluble Flt-1,a key mokecule involving in pathophysiology in cardio-renal connection2008

    • Author(s)
      Onoue K, et. al.
    • Organizer
      The 72^<nd> annual scientific meeting of the Japanese Circulation Society
    • Place of Presentation
      福岡
    • Year and Date
      2008-03-30
    • Related Report
      2007 Annual Research Report
  • [Presentation] JPAD Trial : Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes trial2008

    • Author(s)
      Ogawa H, Uemura S, Saito Y, (and 5 authors)
    • Organizer
      Late-Breaking Clinical Trials-American Heart Association Scientific Session
    • Place of Presentation
      New Orleans, USA
    • Related Report
      2008 Final Research Report
  • [Presentation] Soluble Fms-like Tyrosine Kinase 1 : Decreased Levels Promote Atherosclerosis in Renal Dysfunction while Exogenous Administration Reduces Atherosclerosis Progression2008

    • Author(s)
      Onoue K, Uemura S, Saito Y, (and 13 authors)
    • Organizer
      Late-Breaking Bisic Science-American Heart Association Scientific Session
    • Place of Presentation
      New Orleans, USA
    • Related Report
      2008 Final Research Report
  • [Presentation] Angiogenesis, but not vasculogenesis, palys major role in placental growth factor(PlGF)mediated improvement of cardiac function after myocardial infarction2007

    • Author(s)
      Takeda Y, Uemura S, Saito Y, (and 14 authors)
    • Organizer
      American Heart Association Scientific Session
    • Place of Presentation
      Orlando, USA
    • Related Report
      2008 Final Research Report
  • [Presentation] Plasma Level of Soluble Fms-like Tyrosine Kinase 1(sFlt-1)as a Predictive Marker of Acute Severe Heart Failure in Patients with Acute Myocardial Infarction2007

    • Author(s)
      Onoue K, Uemura S, Saito Y, (and 10 authors)
    • Organizer
      American Heart Association Scientific Session
    • Place of Presentation
      Orlando, USA
    • Related Report
      2008 Final Research Report
  • [Presentation] Soluble Flt-1 is a novel biomarker for the development of severed atherosclerosis in renal dysfunction. Symposium 1. Biomarkers, genetic polymorphism, and risk estimation

    • Author(s)
      Saito Y, Uemura S, (and 8 authors)
    • Organizer
      The 73^<rd> Annual Scientific Meeting of the Japanese Circulation Society
    • Place of Presentation
      Osaka, Japan
    • Related Report
      2008 Final Research Report
  • [Presentation] Tissue characterization of coronary artery in patients with coronary spastic angina by optical coherence tomography. Symposium Coronary Spasm Revisited

    • Author(s)
      Uemura S, Saito Y, (and 5 authors)
    • Organizer
      The 72^<nd> Annual Scientific Meeting of the Japanese Circulation Society
    • Place of Presentation
      Fukuoka, Japan
    • Related Report
      2008 Final Research Report
  • [Book] Annual Review2009循環器. 循環器の生物学3. PlGFと血管新生2009

    • Author(s)
      上村史朗, 斎藤能彦
    • Publisher
      中外医学社
    • Related Report
      2008 Final Research Report
  • [Book] 血管病のモデル-3. 心筋梗塞. 連載 血管病モデルシリーズ2008

    • Author(s)
      上村史朗, 竹田征治, 川田啓之, 斎藤能彦
    • Publisher
      血管医学9(1)
    • Related Report
      2008 Final Research Report
  • [Book] 7. 腎機能障害における動脈硬化進展の機序. 特集 : 腎障害と心疾患-心腎相関を識る-[織る]2008

    • Author(s)
      上村史朗, 斎藤能彦
    • Publisher
      Heart View 12(3)
    • Related Report
      2008 Final Research Report
  • [Book] 慢性腎臓病(CKD)と心血管疾患(CVD)2008

    • Author(s)
      尾上健児, 上村史朗, 斎藤能彦
    • Publisher
      アディポサイエンス5(3)
    • Related Report
      2008 Final Research Report
  • [Remarks]

    • URL

      http://www.naramed-u.ac.jp/~1int/

    • Related Report
      2008 Final Research Report
  • [Remarks]

    • URL

      http://www.naramed-u.ac.jp/~lint/

    • Related Report
      2008 Annual Research Report

URL: 

Published: 2007-04-01   Modified: 2016-04-21  

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