| Project/Area Number |
05044163
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Institution | Kyoto University |
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Principal Investigator |
KITA Toru Kyoto University, Professor, 医学部, 教授 (60161460)
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| Co-Investigator(Kenkyū-buntansha) |
GIMBRONE Mic ハーバード大学, 医学部, 教授
CHAIT Alan University of Washington, Professor, 医学部, 教授
UEDA Yukihiko Kyoto University, Instructor, 医学部, 助手 (70252434)
KUME Noriaki Kyoto University, Instructor, 医学部, 助手 (20252455)
YOKODE Masayuki Kyoto University, Lecturer, 医学部, 講師 (20252447)
GIMBRONE Michael A.jr. Harvard Medical School, Professor
MICHAEL A. G ハーバード大学, 医学部, 教授
ALAN Chait ワシントン州立大学, 医学部, 教授
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| Project Period (FY) |
1993 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥10,000,000 (Direct Cost: ¥10,000,000)
Fiscal Year 1994: ¥5,000,000 (Direct Cost: ¥5,000,000)
Fiscal Year 1993: ¥5,000,000 (Direct Cost: ¥5,000,000)
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| Keywords | familial hypercholesterolemia atherosclerosis / VCAM-1 / WHHL-rabbit / lysophosphatidyl-choline / oxidized LDL / ICAM-1 / T lymphocyte / Tリンパ球 / 粥状動脈硬化 / 血管内皮細胞 / Cキナーゼ |
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| Research Abstract |
Using a new animal model for endogenous hypercholesterolemia, named Watanabe-heritable-hyperlipidemic rabbit, which has a severe fulminant atherosclerosis, we have investigated the sequential expression of monocyteadhesion molecule (VCAM-1), macrophages and T lymphocytes in and on the endothelial monolinear before and after the atherosclerotic lesions covered the space by anti-VCAM-1, macrophage and T lymphocyte antibody respectively. Because our experimental purpose is sequential analysis what is going on the arterial wall in WHHL-rabbit, we chose the place where we examined the expression and existence VCAM-1, macrophage and T lymphocyte, that is the orifice of first branch of intercostal artery. At one month of age WHHL-rabbit, expression of VCAM-1 molecules is observed at the orifice of intercostal artery and covered around the wall at 2 month of age. In addition, at that time, monocytes started to accumulate in the arterial wall, named intimal legion. Three to four weeks later of
… More
this phenomenon T lymphocytes are observed in the same intimal space. In 1987, we reported that antioxidant, probucol, suppressed the progression of atherosclerotic legions in WHHL-rabbit. In 1991, we reported that in the atherosclerotic legions in probucol treated group there were few macrophage derived foam cells than untreated group. to explain these phenomenon we are thinking the possibility which probucol somehow inhibits the expression of VCAM-1 expression in the endothelial cells and this possibility is now under examined. The mechanism why VCAM-1 is induced on the endothelial cell in WHHL rabbit is under investigated in vitro and ICAM-1, another monocyte adhesion molecule, is also examined. Lysophosphatidylcholine (Lyso-PC) which generated in atherosclerotic lesions, has been shown to differentially up regulate VCAM-1 and ICAM-1 expression in various cultured endothelial cells. In case of ICAM-1, induction of this molecules is independent of PMA-regulatable PKC activation but suppressed by increased level of intracellular cyclic AMP.Therefore we focus and put forward on the signal transduction system of Lyso-PC on the expression of ICAM-1 and VCAM-1 collaboration with both Drs. Chait and Gimbrone. Less
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