| Project/Area Number |
13670178
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Human pathology
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| Research Institution | Saga Medical School |
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Principal Investigator |
TOKUNAGA O. Saga Medical School, Department of Pathology, Professor, 医学部, 教授 (40113229)
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| 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)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 2002: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2001: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | ahterosclerosis / Endothelium / SMC / Macrophage / Chlamydia / Herpesviruses / DNA chip / ヘルペスウイルス / 封入体 / マクロファージ / 免疫応答 |
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| 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.
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