| Project/Area Number |
09670142
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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 |
General medical chemistry
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| Research Institution | National Cardiovascular Center Research Institute |
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Principal Investigator |
YOKOYAMA Chieko National Cardiovascular Center Research Institute, Department of Pharmacology, Section Chief, 薬理部, 室長 (90200914)
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| Co-Investigator(Kenkyū-buntansha) |
HATAE Toshihisa National Cardiovascular Center Research Institute, Department of Pharmacology, R, 薬理部, 室員 (10251026)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1998: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1997: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | prostacyclin / prostacyclin synthase / thromboxane A_2 / thromboxane synthase / gene targeting mice / vascular smooth muscle cells / プロスタグランジンI_2 / プロスタサイクリン欠損マウス / ノックアウトマウス |
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| Research Abstract |
Prostacyclin (PGI_2) and thromboxane (TX) A_2 that are lipid bio-factors with potent biological activities in cardiovascular system are involved in diseases such as thrombosis and atherosclerosis. Recentry, we found that both PGI_2 and TX synthases are expressed not only in cardiovascular tissues but also in tissues of the immune system and reproduction. The purpose of this project is to make clear the regulation of PGI_2 and TXA_2 biosynthesis by the analyses of the expression mechanism of PGI_2 and TX synthase genes and to find new biological activities of PGI_2 and TXA_2 with the gene targeting mice of those enzymes. In this study, we have found the results described below.
1. The promoter assay for PGI_2 synthase gene indicated the important promoter regions specific for the transcription in endothelial cells or neointimal vascular smooth muscle cells. 2. Cyclic strain weakly induced gene expression of PGI_2 synthase and cyclooxygenase-2 but not cyclooxygenase-l in bovine endothelial cells. 3. We produced the gene targeting mice of PGI_2 synthase. The mice was completely deficient in PGI_2 and represented their kidney abnormalities with morphological changes. The thickening of the vascular walls, atherosclerosis, and fibrosis were found in the legions. 4. The gene transfer of human PGI_2 synthase-expression vector into rat balloon-injured carotid arteries by HVJ-liposome method resulted in the increased production of PGI_2 in the vascular wall, the expression of human PGI_2 synthase in the developing neointima and significantly inhibited the neointimal formation. 5. We succeeded in the production of TX synthase gene targeting mice.
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