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Development of quantitative analysis method of the atherosclerotic lesions in gene targeted mice

Research Project

Project/Area Number 10557027
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Experimental pathology
Research InstitutionKumamoto University

Principal Investigator

TAKAHASHI Kiyoshi  SCHOOL OF MEDICINE, Kumamoto University, PROF., 医学部, 教授 (70045631)

Co-Investigator(Kenkyū-buntansha) SUZUKI Hiroshi  EXPLORATORY RESEARCH LAB., CHUGAI PHARMACEUTICAL Co. LTD., SENIOR RESEARCHER, 創薬資源研究所, 主任研究員
NAOMI Sakashita  SCHOOL OF MEDICINE, KUMAMOTO UNIVERSITY, ASSISTANT, 医学部, 助手 (90284752)
TAKEYA Motohiro  SCHOOL OF MEDICINE, KUMAMOTO UNIVERSITY, ASSOC. PROF., 医学部, 助教授 (90155052)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1999: ¥2,700,000 (Direct Cost: ¥2,700,000)
Keywordsatherosclerosis / scavenger receptors / gene targeted mice / foam cell formation / morphometry / macrophages / image analysis equipment / anti-oxidant / 泡抹細胞化 / マウス
Research Abstract

One of the most reliable methods for the quantitative analysis of atherosclerotic lesions is direct measurement of the lesion size on tissue sections. In this study, we selected the cross-sections through the aortic valve and ascending aorta where the atherosclerosis occurs at very early stage. Using the aortic valve as a marker, the place of the sectioning is easily oriented. In practice, the four slices crossing aortic valve and ascending aorta were selected, and the area of atherosclerosis in each section was measured by the image analysis microscope system.
Using this method, it was quantitatively proven that the progress of the atherosclerosis in LDL receptor deficient mice was suppressed in the absence of macrophage scavenger receptor (MSR). Other scavenger receptors than MSR such as CD36, MARCO receptor, and CD68/Macrosialin were considered to concern in the lipid uptake of the macrophages at the remaining lesion. This method was also available for the evaluation of anti-atherosclerosis drugs. The measurement showed that a newly developed antioxidant (BO-653) was effective to reduce the atherosclerotic lesion size in ApoE deficient mice.
Though the introduction of the present image analysis microscope system enabled us to carry out the quantitative analysis of the atherosclerosis very conveniently, it has been shown recently that the nature of the atheroma is more concerned to the crisis of the acute coronary syndrome than the degree of stenosis of the artery. Soft atheroma which is rich in macrophages is easy to cause atheroma rupture. From this fact, for the evaluation of the atherosclerosis lesion, it was not sufficient to compare the lesion size only, and it seemed to be important to evaluate the pathological nature of the atheroma itself. This seemed to be the future research subject.

Report

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

    (31 results)

All Other

All Publications (31 results)

  • [Publications] Sakaguchi H et al.: "Role of macrophage scavenger receptors in diet-induced atherosclerosis"Lab Invest. 78. 423-434 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Cynshi O et al.: "Antiatherogenic effects of the antioxidant BO-653 in three different animal models"Proc Natl Acad Sci USA. 95. 10123-10128 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hagiwara S et al.: "Role of macrophage scavenger receptors in hepatic granuloma formation in mice"Am J Pathol. 154. 705-720 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Takeya M et al.: "Macrophage scavenger receptors: structure, function and tissue distribution"Acta Histochem Cytochem. 32. 47-51 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Takaku M et al.: "An in vitro coculture model of transmigrant monocytes and foam cell formation"Arterioscler Thromb Vasc Biol. 19. 2330-2339 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sakashita N et al.: "Localization of acyl-coenzyme A: cholesterol acytransferase (ACAT-1) in macrophages and other various cell types of human tissues"Am J Pathol. 156. 227-236 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sakaguchi H et al.: "Role of macrophage scavenger receptors in diet-induced atherosclerosis in mice"Lab Invest. 78. 423-434 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Honda M et al.: "Immunohistochemical evidence for a macrophage scavenger receptor in Mato cells and reactive microglia of ischemia and Alzheimer's disease"Biochem Biophys Res Comm. 245. 734-740 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Cynshi O et al.: "Antiatherogenic effects of the antioxidant BO-653 in three different animal models"Proc Natl Acad Sci, USA. 95. 10123-10128 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hakamata, H et al.: "The very low- and intermediate-density lipoprotein fraction isolated from apolipoprotein E-knockout mice transforms macrophages to foam cells through an apolipoprotein E-independent pathway"Biochemistry. 37. 13720-13727 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Ling X et al.: "Immunohistochemical distribution and subcellular localization of three distinct specific molecular structure of advanced glycation end products in human tissues"Lab Invest. 78. 1591-1606 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Matsuda H et al.: "Molecular cloning, functional expression and tissue distribution of rat coenzyme A:cholestrol acyltransferase with its activation by acetylated LDL inperitoneal macrophages"Biochem Biomed Acta. 1391. 193-203 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Miyazaki A et al.: "Expression of ACAT-1 protein in human atherosclerotic lesions and in cultured human monocyte-macrophages"Arterioscler Thromb Vasc Biol.. 18. 1568-1574 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yamashiro S et al.: "Intradermal injection of monocyte chemoattractant protein-1 induces emigration and differentiation of blood monocytes in rat Skin"Int Arch Allerg Immunol. 115. 15-23 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hagiwara S et al.: "Role of macrophage scavenger receptors in hepatic granuloma formation in mice"Am J Pathol. 154. 705-720 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Takeya et al.: "Macrophage scavenger receptors: structure, function and tissue distribution (review)"Acta Histochem Cytochem. 32. 47-51 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Kaikita K et al.: "Colocalization of tissue factor and tissue factor pathway inhibitor in coronary atherosclerosis"J Pathol. 188. 180-188 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Takaku M et al.: "An in vitro coculture model of transmigrant monocytes and foam cell formation"Arterioscler Thromb Vasc Biol. 19. 2330-2339 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sakashita N et al.: "Localization of acyl-coenzyme A : cholesterol acytransferase (ACAT-1) in macrophages and other various cell types of human tissues"Am J Pathol. 156. 227-236 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Lehtolainen P et al.: "Retrovirus-mediated, stable scavenger-receptor gene transfer leads to functional endocytotic receptor expression, foam cell formation, and increased susceptibility to apoptosis in rabbit aortic smooth muscle cells"Arterioscler Thromb Vasc Biol. 20. 52-60 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Usui M et al: "Important role of local angiotensin II activity mediated via type 1 receptor in the pathogenesis of cardiovascular inflammatory changes induced by chronic blockade if nitric oxide synthesis in rats"Circulation. 101. 305-310 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Takeya M et al.: "Macrophage scavenger receptors: structure, function and tissue distribution"Acta Histochem Cytochem. 32. 47-51 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kaikita K et al.: "Colocalization of tissue factor and tissue factor pathway inhibitor in coronary atherosclerosis"J Pathol. 188. 180-188 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Takaku M et al.: "An in vitro coculture models of transmigrant monocytes and foam cell formation"Arteriosc Thromb Vasc Biol. 19. 2330-2339 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Sakashita N et al.: "Localization of acyl-coenzyme A: cholesterol acytransferase (ACAT-1) in macrophages and other various cell types of human tissues"Am J Pathol. 156. 227-236 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Lehtolainen P et al.: "Retrovirus-mediated, stable scavenger-receptor gene transfer leads to functional endocytotic receptor expression, foam cell formation, and increased susceptibility to apoptosis in rabbit aortic smooth muscle cells"Arterioscler Thromb Vasc Biol. 20. 52-60 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Sakaguchi H et al.: "Role of macrophage scavenger receptors in diet-induced atherosclerosis" Lav Invest. 78. 423-434 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Cynshi O et al.: "Antiatherogenic effects of the antioxidant BO-653 in three different animal models" Proc Natl Acad Sci USA. 95. 10123-10128 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Honda M et al.: "Immunohistochemical Evidence for a Macrophage Scavenger Receptor in Mato cells and Reactive Microglia of Ischemia and Alzheimer's Disease" Biochem Biophys Res Comm. 245. 734-740 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hagiwara S et al.: "Role of macrophage scavenger receptors in hepatic granuloma formation in mice" Am J Pathol. 154. 705-720 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Takeya M et al.: "Macrophage scavenger receptors: structure,function and tissue distribution" Acta Histochem Cytochem. (in press). (1999)

    • Related Report
      1998 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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