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2002 Fiscal Year Final Research Report Summary

Study of atherosclerosis using DNA microchip

Research Project

Project/Area Number 13670178
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Human pathology
Research InstitutionSaga Medical School

Principal Investigator

TOKUNAGA O.  Saga Medical School, Department of Pathology, Professor, 医学部, 教授 (40113229)

Co-Investigator(Kenkyū-buntansha) YASUNAGA M.  Saga Medical School, Department of Pathology, Research associate, 医学部, 助手 (90325598)
YAMASAKI F.  Saga Medical School, Department of Pathology, Research associate, 医学部, 助手 (80301357)
Project Period (FY) 2001 – 2002
Keywordsahterosclerosis / Endothelium / SMC / Macrophage / Chlamydia / Herpesviruses / DNA chip / ヘルペスウイルス
Research Abstract

The viral nucleic acid of herpes simplex virus type 1 (HSV-1), Epstein-Barn virus (EBV) and Cytomegalovirus (CNV) was studied by polymerase chain reaction, Southern blotting and in situ hybridization in aortic tissues from 33 autopsies. 23 cases ranged from 23 weeks to 75 years of age at the time of death. And the tissue was histologically non-atherosclerotic. 10 cases ranged from 53 years to 75 years old at death were atherosclerotic aortic tissue. Neither double nor triple infections occurred in the non-atherosclerotic group, whereas six of 10 were positive for two viruses, and two of 10 were positive for three viruses in the atherosclerotic group. The viruses were localized in cells morphologically consistent with endothelial cells and smooth muscle cells. Next we investigated both Chlamydia pneumoniae and Chlamydia trachomatis infections. 40% of the tissue examined were positive for C. pneumoniae in contrast to absence in non-atherosclerotic aorta. Elementary bodies of C. pneumoniae were found in macrophage-like cells in the intima of atherosclerotic aorta by electron microscopy. C. trachomatis was not found in both atherosclerotic and non-atherosclerotic aorta.
Based on these results, we further studied the changes of gene expression in cultured endothelial cells, smooth muscle cells and macrophages when they were infected with Herpes virus and C, pneumoniae. Endothelial cells were most susceptible and begin to degenerate lytic 6 hours after the herpes infection. Multinucleated giant cells were formed, but all the cells finally showed lytic after 5 clays of infection. C. pneumoniae infection, however, revealed persistent infection. About 30 genes were expressed high and about 10 genes of them were related to cholesterol metabolism. Heat shock proteins was the most important key gene in relation to infectious agents and antherosclerosis.

  • Research Products

    (17 results)

All Other

All Publications (17 results)

  • [Publications] Tanaka E: "Disparity of MCP-1 mRNA and protein expression between the carotid artery and the aorta in WHHL rabbits"Arterioscler Thromb Vasc biol. 23. 244-250 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shi Y: "Chlamydia pneumoniae and multiple infections in the aorta contribute to atherosclerosis"Pathology International. 52. 755-763 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shi Y: "Herpesvirus (HSV-1, EBV and CMV) infection in athero-sclerotic compared with nosatherosclerotic aortic tissue"Pathology International. 52. 31-39 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tokunaga O: "Multinucleated variant endothelial cells (MVECs) have a greater capacity for LDL cholesterol uptake than typical mononuclear endothelial cells (TECs)"J Athero Thromb. 9(1). 35-41 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Satoh T: "Intracellular oxidative modification of low density lipoprotein by endothelial cells"Virchow Archiv. 441. 88-92 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Chen Y: "Vibrio vulnificus infection in pathients with liver Disease : report of five autopsy cases"Virchow Archiv. 440. 410-417 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 徳永 藏: "第14章 血管内皮細胞のコレステロール移送と細胞内oxidation:高井義美他編集:細胞の形態形成の基本メカニズム"金芳堂. 9 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tanaka E, Shimokawa H, Kamiuneten H, Eto Y, Matsumoto Y, Morishige K, Koike G, Yoshinaga M, Egashira K, Tokunaga O, Shiomi M, Takeshita A: "Disparity of MCP-1mRNA and protein expression between the carotid artery and the aorta in WHHL rabbits"Arterioscler Thromb Vasc biol.. 23. 244-250 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shi Y, Tokunaga O: "Chlamydia pneumoniae and multiple infections in the aorta contribute to atherosclerosis"Pathology International. 52. 755-763 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shi Y, Tokunaga O: "Herpesvirus (HSV-1, EBV and CMV) infection in athero-sclerotic compared with nosatherosclerotic aortic tissue"Pathology International. 52. 31-39 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tokunaga O, Satoh T, Shi Y: "Multinucleated variant endothelial cells (MVECs) have a greater capacity for LDL cholesterol uptake than typical mononuclear endothelial cells (TECs)"J Athero Thromb.. 9(1). 35-41 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Satoh T, Tokunaga O: "Intracellular oxidative modification of low density lipoprotein by endothelial cells"Virchow Archiv.. 441. 88-92 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Chen Y, Satoh T, Tokunaga O: "Vibrio vulnificus infection in patients with liver Disease: report of five autopsy cases"Virchow Archiv.. 440. 410-417 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Fukushima N, Satoh T, Sano M, Tokunaga O: "Angiogenesis and Mast Cells in Non-Hodgkin's Lymphoma: A Strong Correlation in Angioimmunoblastic T-Cell Lymphoma"Leukemia and Lymphoma. 42(4). 709-720 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Chen Y, Satoh T, Sasatomi E, Miyazaki K, Tokunaga O: "Critical Role of Type IV Collagens in the Growth of Bile Duct Carcinoma in Vivo and in Vitro Studies"Pathology Research and Practice. 197. 585-596 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Edakuni G, Sasatomi E, Satoh T, Tokunaga O, Miyazaki K: "Expression of the hepatocyte growth factor/c-Met pathway is increased at the cancer front in breast carcinoma"Pathol. International.. 51. 172-178 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Fukishima N, Satoh T, Sano M, Tokunaga O: "Angiogenesis and Mast Cells in Non-Hodgkin's Lymphoma: A Strong Correlation in Angioimmunoblastic T-Cell Lymphoma"Leukemia and Lymphoma. 42(4). 709-720 (2001)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2004-04-14  

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