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Hypercholesterolemia induces left ventricular hypertrophy and fibrosis via increase of aldosterone biosynthesis.

Research Project

Project/Area Number 15590772
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionJikei University School of Medicine

Principal Investigator

MOCHIZUKI Seibu  Jikei University School of Medicine, Professor, 医学部, 教授 (20130205)

Co-Investigator(Kenkyū-buntansha) IKEWAKI Katsunori  Jikei University School of Medicine, Lecturer, 医学部, 講師 (40287199)
YOSHIDA Hiroshi  Jikei University School of Medicine, Lecturer, 医学部, 講師 (30333529)
YAMANE Teiichi  Jikei University School of Medicine, Lecturer, 医学部, 講師 (40297429)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2003: ¥1,500,000 (Direct Cost: ¥1,500,000)
KeywordsCholesterol / Cardiac hypertrophy / Myocardial Infarction / Aldosterone / Renovascular hypertensive rat / Eprelenone / Cardiac fibrosis / 腎性高血圧ラット
Research Abstract

[Purpose]Supply of cholesterol is essential for biosynthesis of steroid hormones including aldosterone(Aldo). However, it remains to be elucidated that hypercholesterolemia has a direct effect on cardiac hypertrophy and fibrosis. Therefore, we studied whether hypercholesterolemia induces left ventricular(LV) hypertrophy and myocardial fibrosis via increase of Aldo biosynthesis in rabbit model. [Methods]New Zealand white rabbits weighing 3kg were fed a normal chow [control group (C group)] or enriched chow with 2% cholesterol [hypercholesterol group (H group)] for 8 weeks. Plasma concentrations of serum lipids, angiotensin-II(Ang-II), and Aldo were measured. Cardiac diastolic function was evaluated by using echocardiography measuring LV inflow rate. After 8 weeks feeding, hearts were excised and histomorphological analyses were performed.
[Results]High cholesterol diet induced significant increases in total cholesterol and low density lipoprotein cholesterol concentrations. Plasma Aldo concentration was increased and Ang-II concentration was suppressed significantly in H group compared with C group. LV weight/body weight and myocardial fibrosis in H group were also increased compared with C group. In echocardiography, cardiac diastolic function was impaired in H group compared with C group. [Conclusion]The result of our study clearly demonstrates that hypercholesterolemia increases Aldo biosynthesis, induces LV hypertrophy and exerts myocardial fibrosis leading to diastolic dysfunction. Therefore, anti-hypercholesterolemic treatment may contribute to prevent LV hypertrophy and diastolic dysfunction in hypercholesterolemic patients.

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (12 results)

All 2005 2004 Other

All Journal Article (7 results) Publications (5 results)

  • [Journal Article] Hypercholesterolemia induces left ventricular hypertrophy and fibrosis via increase of aldosterone biosynthesis2005

    • Author(s)
      Yuichi Abe et al.
    • Journal Title

      Circulation Journal Vol.69 Suppl.I

      Pages: 467-467

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] The inhibitory effect of eplerenone on left ventricular remodeling after myocardial infarction diminishes in low salt condition2005

    • Author(s)
      Akihiro Urabe et al.
    • Journal Title

      Circulation Journal Vol.69 Suppl.I

      Pages: 360-360

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Hypercholesterolemia induces left ventricular hypertrophy and fibrosis via increase of aldosterone biosynthesis2005

    • Author(s)
      Yuichi Abe et al.
    • Journal Title

      Circulation Journal 69 Suppl.I

      Pages: 467-467

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] The inhibitory effect of eplerenone on left ventricular remodeling after myocardial infarction diminishes in low salt condition2005

    • Author(s)
      Akihiro Urabe et al.
    • Journal Title

      Circulation Journal 69 Suppl.I

      Pages: 360-360

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] A novel two nucleotide deletion in the apolipoprotein A-I gene, apoA-I Shinbashi, associated with high density lipoprotein deficiency, corneal opacities, planar xanthomas, and premature coronay artery disease2004

    • Author(s)
      Katsunori Ikewaki et al.
    • Journal Title

      Atherosclerosis 172

      Pages: 39-45

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Abnormal in vivo metabolism of apoB-containing lipoproteins in human apoE deficiency2004

    • Author(s)
      Katsunori Ikewaki et al.
    • Journal Title

      Journal of Lipid Research Vol.45

      Pages: 1302-1311

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Annual Research Report 2004 Final Research Report Summary
  • [Journal Article] Abnormal in vivo metabolism of apoB-containing lipoproteins in human apoE deficiency2004

    • Author(s)
      Katsunori Ikewaki et al.
    • Journal Title

      Journal of Lipid Research 45

      Pages: 1302-1311

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Date T, Mochizuki S et al.: "Various routes of septal propagation in common atrial flutter"J Interv Card Electrophysiol. 9:3. 317-326 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Seki S, Mochizuki S et al.: "Modulation of intracellular Ca(2+) concentration by tedisamil, a class III antiarrhythmic agent, in isolated heart preparation"Life Sci. 73:14. 1805-1811 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tada N, Yoshida H: "Diacylglycerol on lipid metabolism"Curr Opin Lipidol. 14:1. 29-33 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Seki S, Mochizuki S: "Impaired Ca2+ handling in perfused hypertrophic hearts from Dah1 salt-sensitive rats"Hypertens Res. 26:8. 643-643 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ikewaki K et al.: "A novel two nucleotide deletion in the apolipoprotein A-1 Sninbashi, associated with high density lipoprotein deficiency, cornel opacities, planar xanthomas, and premature coronary artery disease"Atherosclerosis. 172. 39-45 (2004)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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