• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Development of new gene therapy for treatment of atherosclerosis using anti-apoptotic genes

Research Project

Project/Area Number 12670678
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionKYUSHU UNIVERSITY

Principal Investigator

SUGANO Masahiro  Medical Institute of Bioregulation Kyushu Univ. Research Associate, 生体防御医学研究所, 助教授 (20206395)

Co-Investigator(Kenkyū-buntansha) HATAKENAKA Masamitu  Medical Institute of Bioregulation Kyushu Univ. Assistant Professor, 生体防御医学研究所, 講師 (40253413)
MAKINO Naoki  Medical Institute of Bioregulation Kyushu Univ. Professor, 生体防御医学研究所, 教授 (60157170)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2000: ¥2,200,000 (Direct Cost: ¥2,200,000)
KeywordsTumor necrosis factor / Soluble TNF receptor 1 / Apoptosis / Angiogenesis / Endothelial cells / Myocardial infarction / TNF-alphaレセプタ-1 / 酸化LDL
Research Abstract

1) Growth of HUVEC transfected with sTNFRI vector also increased significantly compared to those transfected with control vector. Accumulation of sTNFRI significantly increased in conditioned medium from HUVEC transfected with sTNFRI vector compared to those transfected with control vector. HUVEC transfected with sTNFRI vector not only increased sTNFRI but also prevented shedding of sTNFRI from TNFRI. The TNF-a-induced internucleosomic fragmentation was also significantly prevented in HUVEC transfected with sTNFRI vector compared to those transfected with control vector.
2) The incubation of HUVEC with oxLDL increased LOX-1 mRNA levels and CPP32-like protease activity, and induced apoptosis. Preincubation of HUVEC with nifedipine before incubation with oxLDL significantly suppressed the increase in LOX-1 mRNA levels and CPP32-like protease activity, preventing (7)___ in a dose-dependent manner. These results suggest that nifedipine blocks the suicide pathway leading to the apoptosis of endothelial cells by decreasing LOX-1 mRNA levels and CPP32-like protease activity.
3) Here we report that direct injection of a sTNFRI expression plasmid DNA to the myocardium reduces infarct size in experimental rat AMI. Treatment with sTNFRI expression plasmid DNA reduced the TNF-alpha bioactivity in the myocardium and the apoptosis of cardiomyocytes. These findings suggest that the anti-TNF-alpha therapy by sTNFRI can be a new strategy for treatment of AMI.

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (23 results)

All Other

All Publications (23 results)

  • [Publications] Masahiro Sugano, Keiko Tsuchida, Naoki Makino: "High-density lipoproteins protect endothelial cells from tumor necrosis factor-aloha -induced apoptosis"Biochem Biophys Res Comm.. 272. 872-876 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hiroyoshi Hirayama, Masahiro Sugano, Nobuyuki Abe, Hidetoshi Yonemochi, Naoki Makino: "Determination of left ventricular mass by echocardiography in normotensive diabetic patients"Jpn Circ J.. 64. 921-924 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hiroyoshi Hirayama, Masahiro Sugano, Nobuyuki Abe, Hidetoshi Yonemochi, Naoki Makino: "Troglitazone, an antidiabetic drug, improves left ventricular mass and diastolic function in normotensive diabetic patients"Int J. Cardiol.. 77. 75-79 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Masutomo K., Makino N., Sugano M., Fushiki S.: "Effects of Losartan on the Collagen Degradative Enzymes in Hypertrophic and Congestive types of Cardiomyopathic Hamsters"Mol Cell Biochem.. 224. 19-27 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Masahiro Sugano, Keiko Tsuchida, Hideharu Tomita, Naoki Makino: "Increased proliferation of endothelial cells with overexpression of soluble TNF-a receptor I gene"Atherosclerosis.. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Masahiro Sugano, Keiko Tsuchida, Naoki Makino: "Nifedipine prevents apoptosis of endothelial cells induced by oxidized LDL"J. Cardiovasc Pharmacol.. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Masahiro Sugano, Keiko Tsuchida, Naoki Makino: "High-density lipoproteins protect endothelial cells from tumor necrosis factor-alpha-induced apoptosis"Biochem Biophys Res Comm. 272. 872-876 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hiroyoshi Hirayama, Masahiro Sugano, Nobuyuki Abe, Hidetoshi Yonemochi, Naoki Makino: "Determination of left ventricular mass by echocardiography in normotensive diabetic patients"Jpn Circ J. 64. 921-924 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Hiroyoshi Hirayama, Masahiro Sugano, Nobuyuki Abe, Hidetoshi Yonemochi, Naoki Makino: "Troglitazone, an antidiabetic drug, improves left ventricular mass and diastolic funciton in normotensive diabetic patients"Int J. Cardiol. 77. 75-79 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Masutomo K., Makino N., Sugano M., Fushiki S.: "Effects of Losartan on the Collagen Degradative Enzymes in Hypertrophic and Congestive types of Cardiomyopathic Hamsters"Mol Cell Biochem. 224. 19-27 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Masahiro Sugano, Keiko Tsuchida, Hideharu Tomita, Naoki Makino: "Increased proliferation of endothelial cells with overexpression of soluble TNF-a receptor l gene"Atherosclerosis. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Masahiro Sugano, Keiko Tsuchida, Naoki Makino: "Nifedipine prevents apoptosis of endothelial cells induced by oxidized LDL"J. Cardiovasc Pharmacol. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Masahiro Sugano, Keiko Tsuchida, Naoki Makino: "High-density lipoproteins protect endothelial cells from tumor necrosis factor-alpha-induced apoptosis"Biochem Biophys Res Comm.. 272. 872-876 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hiroyoshi Hirayama, Masahiro Sugano, Nobuyuki Abe, Hidetoshi Yonemochi, Naoki Makino: "Determination of left ventricular mass by echocardiography in normotensive diabetic patients"Jpn Circ J.. 64. 921-924 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hiroyoshi Hirayama, Masahiro Sugano, Nobuyuki Abe, Hidetoshi Yonemochi, Naoki Makino: "Troglitazone, an antidiabetic drug, improves left ventricular mass and diastolic function in normotensive diabetic patients"Int J. Cardiol.. 77. 75-79 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Masutomo K., Makino N., Sugano M., Fushiki S: "Effects of Losartan on the Collagen Degradative Enzymes in Hypertrophic and Congestive types of Cardiomyopathic Hamsters"Mol Cell Biochem.. 224. 19-27 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Masahiro Sugano, Keiko Tsuchida, Hideharu Tomita, Naoki Makino: "Increased proliferation of endothelial cells with overexpression of soluble TNF-a receptor I gene"Atherosclerosis. (in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Masahiro Sugano, Keiko Tsuchida, Naoki Makino: "Nifedipine prevents apoptosis of endothelial cells induced by oxidized LDL"J. Cardiovasc Pharmacol.. (in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Masahiro Sugano,Shojiro Sawada,Keiko Tsuchida,Naoki Makino,Masafumi Kamada.: "Low density lipoproteins develop resistance to oxidative modification due to inhibition of cholesteryl ester transfer protein by a monoclonal antibody"J.Lipid.Res.. 41. 126-133 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Masahiro Sugano,Keiko Tsuchida,Shojiro Sawada,Naoki Makino.: "Reduction of plasma angiotensin II to normal level by antisense oligodeoxynucleotides against liver angiotensinogen can not completely attenuate vascular remodeling in spontaneously hypertensive rats"J.Hypertension.. 18. 725-731 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Masahiro Sugano,Keiko Tsuchida,Naoki Makino.: "High-density lipoproteins protect endothelial cells from tumor necrosis factor-alpha-induced apoptosis."Biochem Biophys Res Comm.. 272. 872-876 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hiroyoshi Hirayama,Masahiro Sugano,Nobuyuki Abe,Hidetoshi Yonemochi,Naoki Makino.: "Determination of left ventricular mass by echocardiography in normotensive diabetic patients."Jpn Circ J.. 64. 921-924 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hiroyoshi Hirayama,Masahiro Sugano,Nobuyuki Abe,Hidetoshi Yonemochi,Naoki Makino.: "Troglitazone, an antidiabetic drug, improves left ventricular mass and diastolic function in normotensive diabetic patients."Int J.Cardiol.. 77. 75-79 (2001)

    • Related Report
      2000 Annual Research Report

URL: 

Published: 2000-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi