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Role of Angiotension and CD36 Expression in Multiple Risk Factors for Atherosclerosis

Research Project

Project/Area Number 17590705
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

NAKAMURA Tetsuya  Gunma University, Clinical Investigation and Research Unit, Associate Professor, 医学部, 助教授 (10272238)

Co-Investigator(Kenkyū-buntansha) KURABAYASHI Masahiko  Gunma University Graduate School of Medicine, Department of Medicine and Biological Science, Professor, 大学院医学系研究科, 教授 (00215047)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2006: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2005: ¥1,900,000 (Direct Cost: ¥1,900,000)
KeywordsHypertension / Insulin resistance / Angiotensin converting enzyme / atherosclerosis / ゲノム / 遺伝子 / 循環器・高血圧 / 老化
Research Abstract

OBJECTIVE : Diiihydropyridine calcium channel blockers (CCB) can prevent the CV events in diabetes. Angiotensin II plays a key role in pathobiological events that lead to vascular disease. The present study examined the long-term effects of CCB and angiotensin II receptor blocker on the cardiovascular protective effects in hypertension.
METHODS and RESULTS : Thirty-week-old male Otsuka Long Evans Tokushima Fatty (OLETF) rates, a model of diabetes with elevated BP, and normal control (Long Evans Tokushima Otsuka : LETO) rats were fed standard chow or chow containing CCB azelnidipine, 0.4 mg/g food (n=15 in each group) for 2 weeks. Angiotensin enzyme (ACE) mRNA in both renal cortex and medulla of OLETF was reduced compared to LETO rats, and further suppressed by azelnidipine. The renal cortical mineralocorticoid receptor (MCR) mRNA in OLETF was higher than in LETO, and reduced significantly by azelnidipine. MCR mRNA in the renal medulla did not differ significantly between 2 strains, and was unaltered by azelnidipine in either strain.
In 46 patients with hypertension, the pulse wave velocity between the brachium and ankle (baPWV) was measured before and 24 weeks after the treatment with valsartan 40 to 160 mg/day. Systolic and diastolic blood pressures were decreased from 155±3 to 140±3 and from 90±2 to 82±2 mmHg, respectively. The baPWV also decreased from 1853±49 cm/sec to 1682 ±52 cm/sec.
CONCLUSION : We demonstrated that azelnidipine normalized the enhanced renal cortical expression of MCR mRNA and reduced renal ACE mRNA in diabetic rats. This is the first report providing that L-type CCB can down-regulated renal expression of ACE and MCR mRNA. We conclude that the treatment effect of valsartan reduces arterial stiffness regardless of baseline blood pressure. Blood pressure reduction alone does not appear to account entirely for the benefits of valsartan therapy on arterial stiffness.

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (19 results)

All 2007 2006 2005

All Journal Article (19 results)

  • [Journal Article] HSF1 and constitutively active HSF1 improve vascular endothelial function (heat shock proteins improve vascular endothelial function).2007

    • Author(s)
      Uchiyama T.
    • Journal Title

      Atherosclerosis 190

      Pages: 321-329

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] HSF1 and constitutively active HSF1 improve vascular endothelial function (heat shock proteins improve vascular endothelial function).2007

    • Author(s)
      Uchiyama T
    • Journal Title

      Atherosclerosis 190

      Pages: 321-329

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Selective angiotensin receptor antagonism with valsartan decreases arterial stiffness independently of blood pressure lowering in hypertensive patients.2006

    • Author(s)
      Kakamura T.
    • Journal Title

      Hypertension Research 28

      Pages: 937-943

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Simvastatin induces heat shock factor 1 in vascular endothelial cells.2006

    • Author(s)
      Uchiyama T.
    • Journal Title

      Atherosclerosis 188

      Pages: 265-273

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Azelnidipine down-regulates renal angiotensin-converting enzyme and mineralocorticoid receptor mRNA in diabetic hypertensive rats.2006

    • Author(s)
      Nakamura T.
    • Journal Title

      Journal of Pharmacological Sciences 102

      Pages: 239-242

    • NAID

      10020345785

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Selective angiotensin receptor antagonism with valsartan decreases arterial stiffness independently of blood pressure lowering in hypertensive patients.2006

    • Author(s)
      Nakamura T
    • Journal Title

      Hypertens Res 28

      Pages: 937-943

    • NAID

      10017403402

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Simvastatin induces heat shock factor 1 in vascular endothelial cells.2006

    • Author(s)
      Uchiyama T
    • Journal Title

      Atherosclerosis 188

      Pages: 265-273

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Azelnidipine down-regulates renal angiotensin-converting enzyme and mineralocorticoid receptor mRNA in diabetic hypertensive rats.2006

    • Author(s)
      Nakamura T
    • Journal Title

      J Pharmacol Sci 102

      Pages: 239-242

    • NAID

      10020345785

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Selective angiotensin receptor antagonism with valsartan decreases arterial stiffness independently of blood pressure lowering in hypertensive patients.2005

    • Author(s)
      Nakamura T.
    • Journal Title

      Hypertension Research 28

      Pages: 937-943

    • NAID

      10017403402

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Fluvastatin ameliorates the hyperhomocysteinemia-induced endothelial dysfunction : the antioxidative properties of fluvastatin.2005

    • Author(s)
      Morita H.
    • Journal Title

      Circulation Journal 69 (4)

      Pages: 475-480

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Effect of transdermal hormone replacement therapy on the monocyte chemoattractant protein-1 concentrations and other vascular inflammatory markers and on endothelial function in postmenopausal women.2005

    • Author(s)
      Sumino H.
    • Journal Title

      American Journal of Cardiology 96

      Pages: 148-153

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary 2005 Annual Research Report
  • [Journal Article] Genotyping of thiopurine methyltransferase using Pyrosequencing.2005

    • Author(s)
      Okada Y.
    • Journal Title

      Biological and Pharmaceutical Bulletin 28 (4)

      Pages: 677-681

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Fluvastatin ameliorates the hyperhomocysteinemia-induced endothelial dysfunction : the antioxidative properties of fluvastatin.2005

    • Author(s)
      Morita H.
    • Journal Title

      Circulation Journal 69

      Pages: 475-480

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Genotyping of thiopurine methyltransferase using pyrosequencing.2005

    • Author(s)
      Okada Y.
    • Journal Title

      Biological and Pharmaceutical Bulletin 28

      Pages: 677-681

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Selective angiotensin receptor antagonism with vaisartan decreases arteria stiffness independently of blood pressure lowering in hypertensive patients.2005

    • Author(s)
      Nakamura T.
    • Journal Title

      Hypertension Research 28

      Pages: 937-943

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Fluvastatin ameliorates the hyperhomocysteinemia-induced endothelial dysfunction : the antioxidative properties of fluvastatin.2005

    • Author(s)
      Morita H.
    • Journal Title

      Circulation Journal 69(4)

      Pages: 475-480

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Genotyping of thiopurine methyltransferase using pyrosequencing.2005

    • Author(s)
      Okada Y.
    • Journal Title

      Biol Pharm Bull 28(4)

      Pages: 677-681

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Comparison of Oral and Transdermal Hormone Replacement Therapy on Arterial Stiffness and Vascular Inflammatory Markers in Postmenopausal Women.2005

    • Author(s)
      Sumino H.
    • Journal Title

      Circulation Journal 69(Suppl 1)

      Pages: 552-552

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Transdermal Hormone Replacement Therapy Reduces Carotid Artery Wall Thickness and Levels of Vascular Inflammatory Markers in Postmenopausal Women.2005

    • Author(s)
      Sumino H.
    • Journal Title

      Circulation Journal 69(Suppl 1)

      Pages: 608-608

    • Related Report
      2005 Annual Research Report

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Published: 2005-04-01   Modified: 2016-04-21  

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