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Role of vascular angiotensin-generating system in atherosclerosis and acute coronary syndrome : Specifoc role of macrophages and smooth muscle cells

Research Project

Project/Area Number 08670791
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

RAKUGI Hiromi  Osaka University Medical School, Assistant Professor, 医学部, 助手 (20252679)

Co-Investigator(Kenkyū-buntansha) UEDA Makiko  Osaka City University, Associate Professor, 医学部, 助教授 (10137193)
OGIHARA Toshio  Osaka University Medical School, Professor, 医学部, 教授 (60107042)
HIGAKI Jituo  Osaka University Medical School, Associate Professor, 医学部, 助教授 (70189744)
Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1997: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1996: ¥1,600,000 (Direct Cost: ¥1,600,000)
Keywordsangiotensin-converting / angiotensin / chymase / ischemic heart disease / immunocytochemistry / macrophages / 遺伝子多型
Research Abstract

Cardioprotective and vasculoprotective effects of angiotensin-converting enzyme (ACE) inhibitors are well reported. To investigate the role of the renin-angiotensin system in atherogenic diseases, we performed immunocytochemical analyzes using human coronary arteries, molecularbiological analysis using cultured macrophages, and genetic analyzes of cerebral infarction and silent myocardial ischemia.
1. In hypercellular lesion and atheromatous plaque, however, enhanced angiotensin II and ACE expression was found in macrophages and smooth muscle cells. Angiotensin type 1 receptor (AT1) was expressed in the adjacent portion of the cap by the rupture site where consist of contractile smooth muscle cells. Fibrosclerotic plaque showed little or no angiotensin II and ACE within the plaque. Enhanced expression of ACE and angiotensin II were found in culprit lesions of patients with unstable angina. Activation of the renin-angiotensin system in the active lesion of coronary atherosclerosis may pl … More ay an important role in the development of atherosclerosis and acute coronary syndrome. Furthermore, AT1 receptor in the intima may contribute to focal vasoconstriction which triggers plaque rupture.
2. The expression of the components of the renin-angiotensin system were investigated in monocytes (THP-1 : a human monocytic leukemia cell line) and macrophages (differentiated THP-1 by adding of PMA). The expression of AT1 and AT2 was detected in monocytes and increased up to 6.3 and 6.5-fold during the differentiation to macrophages. Renin expression and ACE activity were also enhanced during the differentiation. These results suggest that the renin-angiotensin system function via autocrine-paracrine system in macrophages.
3. Homozygous deletion allele (DD) of the ACE gene is known to be associated higher levels of plasma and tissue ACE activities. We investigated the ACE/DD allele was associated with cerebral infarction but not with cerebral hemorrhage. Silent myocardial ischemia did not show association with polymorphism of the ACE gene. Further studies are required to clarify the mechanism of these association. Less

Report

(3 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • Research Products

    (23 results)

All Other

All Publications (23 results)

  • [Publications] Rakugi H: "Recognition of tissue-and subtype-specific modulation of anglotensin II receptors using antibodites against AT1 and AT2 receptors." Hypertens Res. 20. 51-55 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Sato N: "Association of polymorphisms in the critical core promoter element of angiotensinogen gene with increased risk of essential hypertension." Hypertension. 30. 321-325 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nakata Y: "Polymorphism of angiotensin-converting enzyme,angiotensinogen and apolipoprotein E genes in Japanese population with cerebrovascular disease." Am J Hypertens. 10. 1391-1395 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Ohishi M: "Upregulation of angiotensin-converting enzyme during the healing process after injury at the site of percutaneous transluminal coronary angioplasty in humans." Circulation. 96. 3328-3337 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Ohishi M: "Enhanced expression of angiotentin-converting enzy is associated with progression of coronary atherosclerosis in humans." J Hypertens. 15. 1295-1302 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Takami S: "Genetic analysis of angiotensin II receptors : Relationship with severlty of hypertension and left ventricular mass." Am J Hypertens. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Rakugi H.: "Recognition of tissue-and sibtype-specific modulation of angiotensinII receptors using antibodies against AT1 and AT2 receptors." Hypertens Res. 20. 51-55 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Sato N.: "Association of polymorphisms in the critical core promoter element of angiotensinogen gene with increased risk of essential hypertension." Hypertension. 30. 321-325 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nakata Y.: "Polymorphism of angiotensin-converting enzyme, angiotensinogen and apolipoprotein E genes in Japanese population with cerebrovascular disease." Am J Hypertens. 1391-1395 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Ohishi M.: "Upregulation of angiotensin-converting enzyme during the healing process afer injury at the site of percutaneous transluminal coronary angioplasty in humans." Cirulation. 96. 3328-3337 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Ohishi M.: "Enhanced expression of angiotentin-converting enzy is associated with progression of coronary atherosclerosis in humas." J Hypertens. 15. 1295-1302 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Takami S.: "Genetic analysis of angiotensin receptors ; Relationship with severity of hypertension and left ventricular mass." Am J Hypertens. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Rakugi H: "Recognition of tissue- and subtype-specific modulation of angiotensinII receptors using antibodies against AT1 and AT2 receptors." Hypertens Res. 20. 51-55 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Sato N: "Association of polymorphisms in the critical core promoter element of angiotensinogen gene with increased risk of essential hypertension." Hypertension. 30. 321-325 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Nakata Y: "Polymorphism of angiotensin-converting enzyme,angiotensinogen and apolipoprotein E genes in Japanese population with cerebrovascular disease." Am J Hypertens. 10. 1391-1395 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ohishi M: "Upregulation of angiotensin-converting enzyme during the healing process after injury at the site of percutaneous transluminal coronary angioplasty in humans." Circulation. 96. 3328-3337 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ohishi M: "Enhanced expression of angiotentin-converting enzy is associated with progression of coronary atherosclerosis in humans." J Hypertens. 15. 1295-1302 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Takami S: "Genetic analysis of angiotensinII receptors:Relationship with severity of hypertension and left ventricular mass." Am J Hypertens. (in press).

    • Related Report
      1997 Annual Research Report
  • [Publications] Yukiko Nakata: "Polymorphism of the apolipoprotein E and angiotensin-converting enzyme genes in Japanese subjucts with silent myocardial ischemia." Hypertension. 27・6. 1205-1209 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Hiromi RAKUGI: "Links between hypertension and myocardial infarction." American Heart Journal. 132・1(P-12). 213-221 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Seiju TAKAMI: "Analysis and comparison of new candidate loci for hypertension between genetic hypertensive rat strains." Hypertension Research. 19・1. 51-56 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Hiromi RAKUGI: "Recognition of fissue-and subtype-specific modulation of angiotensin II receptors using antibodies against AT_1 and AT_2 receptors." Hypertension Research. (発表予定).

    • Related Report
      1996 Annual Research Report
  • [Publications] Noriyuki SATO: "Association of the polymorphisms in the critical core promoter element of angiotensinogen gene with increased risk of essential hypertension" Hypertension. (発表予定).

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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