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

Essential role of monocyte chemoattractant protein-1 (MCP1) in development of restenotic changes (neointimal hyperplasia and constrictive remodeling) after balloon angioplasty in hypercholesterolemic rabbits

Research Project

Project/Area Number 13671241
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General surgery
Research InstitutionNagoya University (2002)
Kyushu University (2001)

Principal Investigator

KOMORI Kimihiro  Nagoya University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (40225587)

Co-Investigator(Kenkyū-buntansha) MATSUSHITA Masahiro  Nagoya University, Graduate School of Medicine, Associate professor, 大学院・医学系研究科, 助教授 (70273240)
KOBAYASHI Masayoshi  Nagoya University, University Hospital, Research Associate, 医学部附属病院, 助手 (60329381)
NISHIKIMI Naomichi  Nagoya University, University Hospital, Assistant Professor, 医学部附属病院, 講師 (40242862)
YONEMITSU Yoshikazu  Kyushu University, Graduate School of Medicine, Research Associate, 大学院・医学系研究科, 助手 (40315065)
古山 正  九州大学, 医学部・附属病院, 医員(臨床)
庄司 哲也  九州大学, 医学部・附属病院, 医員(臨床)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2001: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywordsintimal thickening / MCP-1 / gene therapy / late graft failure / 血管内膜肥厚
Research Abstract

Although grafting with an autologous vein as a vascular substitute in the treatment of peripheral arterial occlusive disease is the surgical procedure that yields the best long-term results, late vein graft failure remains a significant problem for vascular surgeons. Infiltration and activation of monocytes in, the arterial wall mediated by monocyte chemoattractant protein-1 (MCP-1) might be a major cause of restenosis after angioplasty. However, there is no direct evidence to support a definite role of MCP-1 in the development of restenosis.
We recently devised a new strategy for anti-MCP-1 gene therapy by transfecting an N-terminal deletion. mutant of the MCP-1 gene into skeletal muscles.
We found that after balloon injury, the MCP-1 mRNA level significantly increased as early as day 1, but declined with time ; at all points in time, however, gene expression of MCP-1 in the injured artery was significantly higher on days 3, 7, and 28 than that in the noninjured control artery. Appearance of RAM11-positive macrophages were not distinct on day 1, but became evident on days 3, 7, and 28. We found that 7ND gene transfer markedly suppressed macrophage infiltration into the intima, media, and adventitia after balloon injury.
We found that intimal area and intima/media ratio were less in 7ND group than in PBS or empty plasmid group and that negative remodeling (smaller lumen size, IEL and EEL) was less in 7ND group than in PBS or empty plasmid group. As a result of the inhibition of neointimal formation and negative remodeling, luminal narrowing was prevented.
MCP-1-mediated monocyte infiltration is necessary in the development of restenotic changes to balloon injury in hypercholesterolemic rabbits. This strategy may be a useful and practical form of gene therapy against human restenosis.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] Ishida M: "Immunohistochemical phenotipic alterations of rabbit autologous vein grafts implanted under arterial circulation with or without poor distal runoff-implications of vein graft remodeling-"Atherosclerosis. 154. 345-354 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Matsumoto T: "Successful and optimized in vivo gene transfer to rabbit carotid artery mediated by electronic pulse"Gene Therapy. 8. 1174-1179 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ohta S: "Intraluminal gene transfer of endothelial cell-nitric oxide synthase suppresses intimal hyperplasia of vein grafts in cholesterol-fed rabbit : a limited biological effect as a result of the loss of medial smooth muscle cells"Surgery. 131(6). 644-653 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mori E: "Essential role of monocyte chemoattractant protein-1 in development of restenotic changes (neointimal hyperplasia and constrictive remodeling) after balloon angioplasty in hypercholesterolemic rabbits"Circulation. 105(24). 2905-2910 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kume M: "Administration of a decoy against the activator protein-1 binding site suppresses neointimal thickening in rabbit balloon-injured arteries"Circulation. 105(10). 1226-1232 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Komori K: "Differences in endothelial function and morphologic modulation between canine autogenous venous and arterial grafts : endothelium and intimal thickening"Surgery. 131. 249-255 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ishida M: "Immunohistochemical phenotipic alterations of rabbit autologous vein grafts implanted under arterial circulation with or without poor distal runoff-implications of vein graft remodeling-"Atherosclerosis. 154. 345-354 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Matsumoto T: "Successful and optimized in vivo gene transfer to rabbit carotid artery mediated by electronic pulse"Gene Therapy. 8. 1174-1179 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ohta S: "Intraluminal gene transfer of endothelial cell-nitric oxide synthase suppresses intimal hyperplasia of vein grafts in cholesterol-fed rabbit : a limited biological effect as a result of the loss of medial smooth muscle cells"Surgery. 131 (6). 644-653 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mori E: "Essential role of monocyte chemoattractant protein-1 in development of restenotic changes (neointimal hyperplasia and constrictive remodeling) after balloon angioplasty in hypercholesterolemic rabbits"Circulation. 105 (24). 2905-2910 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kume M: "Administration of a decoy against the activator protein-1 binding site suppresses neointimal thickening in rabbit balloon-injured arteries"Circulation. 105 (10). 1226-1232 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Komori K: "Differences in endothelial function and morphologic modulation between canine autogenous venous and arterial grafts : endothelium and intimal thickening"Surgery. 131. 249-255 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ohta S: "Intraluminal gene transfer of endothelial cell-nitric oxide synthase suppresses intimal hyperplasia of vein grafts in cholesterol-fed rabbit : a limited biological effect as a result of the loss of medial smooth muscle cells"Surgery. 131(6). 644-653 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Mori E: "Essential role of monocyte chemoattractant protein-1 in development of restenotic changes (neointimal hyperplasia and constrictive remodeling) after balloon angioplasty in hypercholesterolemic rabbits"Circulation. 105(24). 2905-2910 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kume M: "Administration of a decoy against the activator protein-1 binding site suppresses neointimal thickening in rabbit balloon-injured arteries"Circulation. 105(10). 1226-1232 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Mori E: "Comparison of the long-term results between surgical and conservative treatment in patients with intermittent claudication"Surgery. 131. 269-274 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Onohara T: "Local blood serotonin and soluble P-selectin levels during percutaneous transluminal balloon angioplasty and primary stenting of the iliac artery"Surgery. 131. 256-260 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Komori K: "Differences in endothelial function and morphologic modulation between canine autogenous venous and arterial grafts : endothelium and intimal thickening"Surgery. 131. 249-255 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Komori K, Shoji T, Furuyama T, Yonemitsu Y, Mori E, Yamaoka T, Matsumoto T, Sugimachi K: "Nonpenetrating vascular clips anastomosis inhibited intimal thcikening under poor runoff conditions in canine autogenous vein grafts"Eur J Vasc End Surg. 21. 241-247 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Komori K, Furuyama T, Shoji T, Kume M, Mori E, yamaoka T, Sugimachi K.: "Inhibitory effect of prostaglandin E1 in intimal thickening caused by poor runoff conditions in the canine autogenous vein grafts"J Cardiovasc Pharmacol. 38. 686-692 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ishida M, Komori K, Yonemitsu Y, Matsumoto T, Onohara T, Sugimachi K.: "Immunohistochemical phenotipic alterations of rabbit autologous vein grafts implanted under arterial circulation with or without poor distal run off-implications of vein graft remodeling-"Atherosclerosis. 154. 345-354 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Wei CG, Komori K, Mori E, Kume M, Yamaoka T, Matsumoto T, Sugiamchi K.: "Natural course of the functional and morphological changes in canine autogenous arterial graft"Eur Surg Res. 33. 21-27 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Matsumoto T, Komori K, Shoji T, Kuma S, Kume M, Yamaoka T, Mori E, Furuyama T, Yonemitsu Y, Sugimachi K:: "Successful and optimized in vivo gene transfer to rabbit carotid artery mediated by electronic pulse"Gene Therapy. 8. 1174-1179 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Masaki I, Yonemitsu Y, Komori K, Ueno H, Nakashima Y, Nakagawa K, Fukumura M, Kato A, Hasan MK, Nagai Y, Sugimachi K, Hasegawa M, Suishi K:: "Reconbinant Sendal virus-mediated gene transfer to vasculature: a new class of efficient gene transfer vector to the vascular system"FASEB Journal. 15. 1294-1296 (2001)

    • Related Report
      2001 Annual Research Report

URL: 

Published: 2001-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi