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Role of chylomicron remnants in vascular remodeling

Research Project

Project/Area Number 13670711
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

Principal Investigator

ISHIKAWA Yuichi  Kobe University Graduate School of Medicine, Division of Health Sciences, Professor, 医学部, 教授 (90159707)

Co-Investigator(Kenkyū-buntansha) KAWASHIMA Seinosuke  Kobe University Graduate School of Medicine, Division of Cardiovascular and Respiratory Medicine, Department of Intemal Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (10177678)
TANIGUCHI Takahiro  Kobe University Graduate School of Medicine, Division of Cardiovascular and Respiratory Medicine, Department of Intemal Medicine, Assistant Professor, 大学院・医学系研究科, 講師 (20263379)
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: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2001: ¥1,900,000 (Direct Cost: ¥1,900,000)
Keywordschylomicron remnants / endothelial cells / vascular smooth muscle cell / apoptosis / monocyte chemoattractant protein 1 / 血管内非細胞 / 血管平滑筋細胞 / アポートシス / 細胞内シグナル伝達
Research Abstract

All forms of percutaneous coronary intervention confer injury on the vessel. The arterial response to that injury is the basis for long-term outcome. Neointima forms in response to thrombus, inflammation, intimal and medial dissections, and elastic recoil of the arterial wall when augioplasry was performed. Chylomicron remnants, major lipoproteins at postprandial hyperlipidemia, is considered to be proatherogenic lipoproteins. However, the mechanisms by which chylomicron remnants enhance atherosclerosis have not been fully understood. Here, we examined the effect of chylomicron remnants on endothelial cells and smooth muscle cells. We prepared chylomicrons from the lymph of the rats which were fed with egg solution and obtained chylomicron remnants from the plasma of functionally hepatectomized rats injected with chylomicrons. First, we examined the effect of chylomicron remnants on human umbilical vein endomelial cells (HUVECs). Chylomicron remnants activated caspase-3 activity and in … More duced apoptosis of HUVECs in a dose dependent manner. Next, we investigated the effect of chylomicron remnants on monocyte chemoattractant protein-1 (MCP-1) expression in cultured vascular smooth muscle cells (VSMCs). MCP-1 is a chemokine, which stimulates migration of monocytes and plays a critical role in the development of atherosclerosis. Treatment of VSMC with chylomicron remnants significantly increased the expression of MCP-1 mRNA and protein in a time-and dose-dependent manner. Furthermore, chylomicron remnants activated p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK1/2). Pretreatment of VSMCs with p38 MAPK inhibitors,SB203580 and SB202190, dose-dependently inhibited chylomicron remnants-induced MCP-1 mRNA and protein expression,whereas a MAPK kinase inhibitor (PD98059) had no effect on these responses. Chylomicron remnants-induced MCP-1 secretion into the media was much more pronounced than those induced by chylomicrons, oxidized low-density lipoproteins, or lysophosphatidylcholine. Ohylomicron remnants may exacerbate atherosclerosis by inducing endothelial cell apoptosis and stimulating MCP-1 expression in VSMCs. Less

Report

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

Research Products

(20 results)

All Other

All Publications (20 results)

  • [Publications] 谷口 隆弘: "レムナントと動脈硬化"Athero-thrombosis. 7・1. 36-38 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 谷口 隆弘: "冠動脈形成術後再狭窄の薬物療法"Molecular Medicine. 38. 281-286 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 高橋 知三郎: "スタチンの種類とPleiotropic Effectの差異"Geriatric Medicine. 39・4. 595-599 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Akihiko Oda: "Leptin stimulates rat aortic smooth muscle cell proliferation and migration"Kobe Journal of Medical Sciences. 47. 201-207 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Seinosuke Kawashima: "Endothelial NO synthase overexpression inhibits lesion formation in mouse model of vascular remodeling"Arterioscler Thromb Vasc Biol.. 21. 201-207 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Seinosuke Kawashima: "A HMG-CoA reductase inhibitor reduces stroke events in stroke-prone spontaneously hypertensive rats"Stroke. 34・1. 157-163 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Taniguchi T: "Remnants and atherosclerosis"Athero-thrombosis. 7(1). 36-38 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Taniguchi T: "Drug therapy for coronary angioplasty"Molecular Medicine. 38. 281-286 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takahashi T: "Pleiotropic effect of statins"Geriatric Medicine. 39(4). 595-599 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Oda A, Taniguchi T and Yokoyama M.: "Leptin stimulatesrat aortic smooth muscle cell proliferation and migration"Kobe J. Med. Sci. 47. 141-150 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawashima S, Yamashita T, Ozaki M, Ohashi Y, Azumi H, Inoue N, Hirata K, Hayashi Y, Itoh H, Yokoyama M.: "Endothelial NO synthase overexpression inhibits lesion formation in mouse model of vascular remodeling"Arterioscler Thromb Vasc Biol. 21(2). 201-207 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sata M, Takahashi A, Tanaka K, Washida M, Ishizaka N, Ako J, Yoshizumi M, Ouchi Y, Taniguchi T, Hirata Y, Yokoyama M, Nagai R, Walsh K.: "Mouse genetic evidence that tranilast reduces smooth muscle cell hyperplasia via a p21 (WAF1)-dependent pathway"Arterioscler Thromb Vasc Biol 2002 Aug 1. 22(8). 1305-1309

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawashima S, Yamashita T, Miwa Y, Ozaki M, Namiki M, Hirase T, Inoue N, Hirata K, Yokoyama M.: "HMG-CoA reductase inhibitor has protective effects against stroke events in stroke-prone spontaneously hypertensive rats"Stroke 2003 Jan. 34(1). 157-163

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takaishi H, Taniguchi T, Takahashi A, Ishikawa Y, Yokoyama M.: "High glucose accelerates MCP-1 production via p38 MAPK in vascular endothelial cells"Biochem Biophys Res Commun 2003 May 23. 305(1). 122-128

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 谷口 隆弘: "レムナントと動脈硬化"Athero-thrombosis. 7・1. 36-38 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] 谷口 隆弘: "冠動脈形成術後再狭窄の薬物療法"Molecular Medicine. 38. 281-286 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] 高橋 知三郎: "スタチンの種類とPleiotropic Effectsの差異"Geriatric Medicine. 39・4. 595-599 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Akihiko Oda: "Leptin stimulates rat aortic smooth muscle cell proliferation and migration"Kobe Journal of Medical Sciences. 47. 141-150 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Seinosuke Kawashima: "Endothelial NO synthase overexpression inhibits lesion formation in mouse model of vascular remodeling"Arterioscier Thromb Vasc Biol.. 21. 201-207 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Seinosuke Kawashima: "A HMG-CoA reductase inhibitor reduces stroke events in stroke-prone spontaneously hypertensive rats"Stroke. 34・1. 157-163 (2003)

    • Related Report
      2002 Annual Research Report

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Published: 2001-03-31   Modified: 2016-04-21  

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