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Regulation by Leptin of Vascular Smooth Muscle Cells Proliferation and Migration

Research Project

Project/Area Number 10670657
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

ISHIKAWA Yuichi  Kobe University School of Medicine, Faculty of Health Science, Professor, 医学部, 教授 (90159707)

Co-Investigator(Kenkyū-buntansha) KAWASHIMA Seinosuke  Kobe University School of Medicine, First Department of Internal Medicine, Associate Professor, 医学部・附属病院, 講師 (10177678)
TANIGUCHI Takahiro  Kobe University School of Medicine, First Department of Internal Medicine, Associate Professor, 医学部・附属病院, 講師 (20263379)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 1999: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1998: ¥2,300,000 (Direct Cost: ¥2,300,000)
KeywordsLeptin / Vascular Smooth Muscle Cells / Proliferation / Migration / Signal Transduction / MAP kinase / PI 3-kinase / 動脈硬化 / 血管形成術後再挟窄 / 細胞増殖
Research Abstract

Obesity is one of the major risk factors for cardiovascular diseases. However, less is yet known about the molecular mechanisms associating between obesity and cardiovascular diseases. The ob gene product, leptin has been defined as a regulator of food intake and energy expenditure. The receptors for leptin (OB-R) are widely expressed throughout the body, suggesting that, in addition to the control of food intake and body weight, leptin may have other important physiological functions. In obese patients, plasma leptin levels are elevated. Therefore, in this study, we investigated the effect of leptin on vascular smooth muscle cell (VSMC) functions. Cultured rat aortic VSMC expressed several isoforms of leptin receptors including 130-kDa short form. Leptin stimulated both proliferation and migration of VSMC. Leptin stimulated phosphorylation and activation of extracellular-regulated Kinase (ERK) isoformes of mitogen-activated protein (MAP) kinases, and also increased phosphatidylinositol (PI) 3-kinase activity in anti-phosphotyrosine immunoprecipitates in VSMC. Further, two distinct PI 3-kinase inhibitors, wortmannin and LY294002 inhibited the migratory effect of leptin, indicating the essential role of PI 3-kinase in leptin-stimulated migration of VSMC. These results demonstrate that leptin is a proliferative and migratory factor for VSMC, implying that leptin plays a role in the formation and development of vascular lesions.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report

Research Products

(29 results)

All Other

All Publications (29 results)

  • [Publications] Akihiro Takahashi: "Tranilast inhibits vascular smooth muscle cell growth and intimal hyperplasia b induction of p21 waf1/cip1/Sdi1 and p53"Circulation Research. 84. 543-550 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tomosaburo Takahashi: "Activation of Akt/protein kinase B after simulation with angiotensin II in vascular smooth muscle cells"American Journal of physiology. 276. H1927-H1934 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Naoya Watanabe: "Elevated Remnant-Like Lipoprotein Particles in Impaired Glucose Tolerance and Type 2 Diabetic Patients"Diabetes Care. 22. 152-156 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] A. Hijikata-Okunomiya: "Effect of Argatroban on Thrombin-induced Events in Cultured Vascular Smooth Muscle Cells"Thrombosis Research. 97. 257-262 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Makoto Watanabe: "Immunohistochemical Analysis of Lipoprotein (a) Deposition and Inflammatory Cells in Coronary Atherosclerosis"Acta Histochem. Cytochem.. 31. 49-54 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yuichi Ishikawa: "The Plasma Levels of Leptin were Correlated with the Metabolic Cardiovascular Risk Factors such as Obesity and Dyslipidemias in Healthy Subjects"Bulletin of Health Science Kobe. 15. 21-25 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 谷口 隆弘: "治療学"イコサペント酸エチルによる治療の意義. 4 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 石川 雄一: "からだの科学"適正体重を考える. 5 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] T.Takahashi: "Tyrosine phosphorylation and association of p130ィイD1CasィエD1 and c-Crk II by ANG II in vascular smooth muscle cells"American Journal of Physiology. 43. H1059-H1065 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] M.Watanabe: "Immunohistochemical Analysis of Lipoprotein(a) Deposition and Inflammatory Cells in Coronary Atherosclerosis"Acta Histochem. Cytochem. 31. 49-54 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Y.Ishikawa: "The relationship of central circulation and peripheral circulation during exercise in patients with chronic heart failure"Bulletin of Health Science Kobe. 14. 57-64 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] A.Hijikata-Okunomiya: "Inhibitory effect of argatoroban on thrombin-induced MAP kinase activation"Thromb. Haemost. 80. 528-529 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] T.Muraki: "Effect of aging on ventilatory function in elderly male community-dwelling subjects"Bulletin of Health Science Kobe. 14. 35-41 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] A.Takahashi: "Tranilast inhibits vascular smooth muscle cell growth and intimal hyperplasia by induction of p21waf1/cip1/Sdi1 and p53"Circulation Research. 84. 543-550 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] T.Takahashi: "Activation of Akt/Protein Kinase B Following Stimulation with Angiotensin II in Vascular Smooth Muscle Cells"American Journal of Physiology. 276. H1927-H1934 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] N.Watanabe: "Elevated Remnant-Like Lipoprotein Particles in Impaired Glucose Tolerance and Type 2 Diabetic Patients"Diabetes Care. 22. 152-156 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Y.Ishikawa: "The plasma levels of leptin were correlated with the metabolic cardiovascular risk factors such as obesity and dyslipidemias in healthy subjects"Bulletin of Health Science Kobe. 15. 21-25 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] T.Muraki: "Psychological effects of ascending and descending stairs on cardiometabolic function in the hemiparetic elderly"Physical & Occupational Therapy in Geriatrics. 16. 65-76 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] A.Hijikata-Okunomiya: "Effect of Argatroban on Thrombin-induced Events in Cultured Vascular Smooth Muscle Cells"Thrombosis Research. 97. 257-262 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] T.Takahashi: "Participation of reactive oxygen intermediates in the angiotensin II-activated signaling pathways in vascular smooth muscle cells"Ann. N. Y. Acad. Sci.. (in press). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] S.Kawasaki: "Chylomicron remnant induces apoptosis in bovine aortic endothelial cells"Ann. N. Y. Acad. Sci.. (in press). (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Akihiro Takahashi: "Tranilast inhibits vascular smooth muscle cell growth and intimal hyperplasia by induction of p21waf1/cip1/Sdi1 and p53"Circulation Risearch. 84. 543-550 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tomosaburo Takahashi: "Acitivation of Akt/protein kinase B after stimulation with angiotensin II in vascular smooth muscle cells"American Journal of Physiology. 276. H1927-H1934 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Naoya Watanabe: "Elevated Remnant-Like Lipoprotein Particles in Impaired Glucose Tolerance and Type 2 Diabetic Patients"Diabetes Care. 22. 152-156 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Makoto Watanabe: "Immunohistochemical Analysis of Lipoprotein(a) Deposition and Inflammatory Cells in Coronary Atherosclerosis"Acta Histochem.Cytochem.. 31. 49-54 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] A.Hijikata-Okunomiya: "Effect of Argatroban on Thrombin-induced Events in Cultured Vascular Smooth Muscle Cells"Thrombosis Research. 97. 257-262 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yuichi Ishikawa: "The Plasma Levels of Leptin were Correlated with the Metabolic Cardiovascular Risk Factors such as Obesity and Dyslipidemias in Healthy Subjects"Bulletin of Health Sciences Kobe. 15. 21-25 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 谷口隆弘: "治療学"イコサペント酸エチルによる治療の意義. 4 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 石川雄一: "からだの科学"適正体重を考える. 5 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1998-03-31   Modified: 2016-04-21  

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