Project/Area Number |
04454181
|
Research Category |
Grant-in-Aid for General Scientific Research (B)
|
Allocation Type | Single-year Grants |
Research Field |
Human pathology
|
Research Institution | University of Tsukuba |
Principal Investigator |
WATANABE Teruo Inst.Basic M.Sci., University of Tsukuba Professor, 基礎医学系, 教授 (40037396)
|
Co-Investigator(Kenkyū-buntansha) |
SHIMOKAMA Tatsuro Inst.Basic M.Sci., University of Tasukuba Assist.Prof., 基礎医学系, 講師 (50170999)
菅間 博 筑波大学, 基礎医学系, 講師 (10195191)
|
Project Period (FY) |
1992 – 1994
|
Project Status |
Completed (Fiscal Year 1994)
|
Budget Amount *help |
¥5,600,000 (Direct Cost: ¥5,600,000)
Fiscal Year 1994: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1993: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1992: ¥2,700,000 (Direct Cost: ¥2,700,000)
|
Keywords | Atherogenesis / Atherosclerosis / Macrophages / T lymphocytes / Immune Mechanism / Foam Cells / In Vitro Model / Hypercholesterolemia |
Research Abstract |
(1) To elucidate the role of T lymphcytes and macrophages in human atherosclerosis, the localization of various cytokines with an analysis of immunophenotypic featues of the cellular initlrates was studied in normal aortas from children and in later phases of the disease, and the results suggested that a specific in situ, cell mediated hypersensitivity plays a pivotal role in the nascent as well as the progression stages of human atherogenesis. (2) Temporal and spatial distribution of the immunologic components of atherosclerosis was studied in a diet-induced rat model. Analysis of cellular components by en face double immunostaining revealded that infiltration of T lymphocytes was most prominent in the incipient phase of lesion formation. (3) In vivo functions of T lymphocytes relevant to atherogenesis was studied in diet-induced aortic lesions of athymic nude rats lacking T lymphocytes, and the results obtained demonstrated that, in comparison with control animals, the lesion development was limited in size, whereas foam cell transformation of intimal macrophages was more prominent in nude rats. (4) We developed an in vitro model of the arterial intima for three dimensional analysis of vascular cell interactions relevant to atherogenesis, and ; induced fatty streak-like lesions by the use of blood mononulcear cells snd endothelial cell-modified low density lipoprotein.
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