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MOLECULAR MECHANISM OF ADIPONECTIN-DEFICIENCY ON HYPERTENSION AND CARDIVASCULAR REMODELING

Research Project

Project/Area Number 17590960
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Endocrinology
Research InstitutionOsaka University

Principal Investigator

KIHARA Shinji  OSAKA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, ASSISTANT, 医学系研究科, 助手 (20332736)

Co-Investigator(Kenkyū-buntansha) NAKAMURA Tadashi  OSAKA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, ASSISTANT PROFESSOR, 医学系研究科, 講師 (90252668)
FUNAHASHI Tohru  OSAKA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, ASSOCIATE PROFESSOR, 医学系研究科, 助教授 (60243234)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2005: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsGENE / INTERNAL MEDICINE / CARDIOVASCULAR / HYPERTENSION / DIABETES MELLITUS / PROTEOME
Research Abstract

This study was designed to elucidate the molecular mechanism of hypoadiponectinemia on the development of hypertension and cardiovascular remodeling with adiponectin deficient mice. Adiponectin deficient mice developed hypertension when maintained on a high-salt diet without insulin resistance. The hypertension of salt-fed adiponectin deficient mice was associated with the impaired induction of endothelial NO synthase mRNA level in the systemic vasculature. Adiponectin therapy lowered the elevated blood pressure and increased endothelial NO synthase. Ischemia-reperfusion in adiponectin deficient mice resulted in increased myocardial infarct size. Administration of adiponectin diminished infarct size. Adiponectin suppressed myocardial apoptosis and tumor necrosis factor-alpha expression through AMP-activated protein kinase and cyclooxygenase pathways, respectively. In human aortic endothelial cells, adiponectin suppressed inflammatory cytokine IL-8 production, which may mediate adiponectin inhibition of atherosclerosis. In addition, as clinical significance of adiponectin, we found that 1) Angiotensin II type-1 receptor blocker increased plasma adiponectin level by targeting oxidative stress in adipose tissue, 2) Smoking habit was associated decreased adiponectin level, and oxidative stress and nicotine reduced adiponectin mRNA in adipocytes, 3) Thiazolidinedione treatment improved left ventricular diastolic function without left ventricular mass regression in hypertensive patients in proportion to the amelioration of insulin resistance, 4) Adiponectin was decreased in patients with peripheral arterial occlusive disease in proportion to the severity of the disease, 5) Renal function was a significant regulator of adiponectin when categorized by chronic kidney disease stages, whereas hypoadiponectinemia was a predictor of cardiovascular disease. These results provide an adiponectin mediated novel molecular basis of hypertension and cardiovascular remodeling.

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] Association of adiponectin and resistin with cardiovascular events in Korean patients with type 2 diabetes2007

    • Author(s)
      Lim S
    • Journal Title

      Atherosclerosis (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Association of adiponectin and resistin with cardiovascular events in Korean patients with type 2 diabetes2007

    • Author(s)
      Lim S
    • Journal Title

      Atherosclerosis (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Adiponectin replenishment ameliorates obesity-related hypertension2006

    • Author(s)
      Ohashi K
    • Journal Title

      Hypertension 47(6)

      Pages: 1108-1116

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Blockade of Angiotensin II type-1 receptor reduces oxidative stress in adipose tissue and ameliorates adipocytokine dysregulation2006

    • Author(s)
      Kurata A
    • Journal Title

      Kidney Int. 70(10)

      Pages: 1717-1724

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Adiponectin and renal function, and implication as a risk of cardiovascular disease2006

    • Author(s)
      Iwashima Y
    • Journal Title

      Am J Cardiol. 98(12)

      Pages: 1603-1608

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Effect of adiponectin on murine colitis induced by dextran sulfate sodium2006

    • Author(s)
      Nishihara T
    • Journal Title

      Gastroenterology 31(3)

      Pages: 853-861

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Identification of amino-terminal region of adiponectin as a physiologically functional domain2006

    • Author(s)
      Ujiie H
    • Journal Title

      J Cell Biochem. 98(1)

      Pages: 194-207

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Adiponectin and inflammatory markers in peripheral arterial occlusive disease2006

    • Author(s)
      Iwashima Y
    • Journal Title

      Atherosclerosis 188(2)

      Pages: 384-390

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Adiponectin deficiency exacerbates lipopolysaccharide/D-galactosamine-induced liver injury in mice2006

    • Author(s)
      Matsumoto H
    • Journal Title

      World J Gastroenterol. 12(21)

      Pages: 3352-3358

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Adiponectin deficiency exacerbates lipopolysaccharide/ D-galactosamine-induced liver injury in mice2006

    • Author(s)
      Matsumoto H
    • Journal Title

      World J Gastroenterol. 12(21)

      Pages: 3352-3358

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Adiponectin protects against myocardial ischemia-reperfusion injury through AMPK-and COX-2-dependent mechanisms.2005

    • Author(s)
      Shibata R
    • Journal Title

      Nat Med. 11(10)

      Pages: 1096-1103

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Adiponectin inhibits endothelial synthesis of interleukin-8.2005

    • Author(s)
      Kobashi C
    • Journal Title

      Circ Res. 97(12)

      Pages: 1245-1252

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Association of hypoadiponectinemia with smoking habit in men.2005

    • Author(s)
      Iwashima Y
    • Journal Title

      Hypertension 45(6)

      Pages: 1094-1100

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Pioglitazone improves left ventricular diastolic function in patients with essential hypertension.2005

    • Author(s)
      Horio T
    • Journal Title

      Am J Hypertens. 18(7)

      Pages: 949-957

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Production of adiponectin, an anti-inflammatory protein, in mesenteric adipose tissue in Crohn's disease2005

    • Author(s)
      Yamamoto K
    • Journal Title

      Gut 54(6)

      Pages: 789-796

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Association of hypoadiponectinemia with smoking habit in men2005

    • Author(s)
      Iwashima Y
    • Journal Title

      Hypertension 45(6)

      Pages: 1094-100

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary 2005 Annual Research Report
  • [Journal Article] Adiponectin protects against myocardial ischemia-reperfusion injury through AMPK- and COX-2-dependent mechanisms2005

    • Author(s)
      Shibata R
    • Journal Title

      Nat Med 11(10)

      Pages: 1096-1103

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Adiponectin inhibits endothelial synthesis of interleukin-82005

    • Author(s)
      Kobashi C
    • Journal Title

      Circ Res. 97(12)

      Pages: 1245-1252

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Pioglitazone improves left ventricular diastolic function in patients with essential hypertension.2005

    • Author(s)
      Horio T
    • Journal Title

      Am J Hypertens 18(7)

      Pages: 949-957

    • Related Report
      2005 Annual Research Report

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

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