| Project/Area Number |
12671121
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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 |
Metabolomics
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| Research Institution | Osaka City University |
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Principal Investigator |
SHIOI Atushi Osaka City University, Graduate School of Medicine, Lecturer, 大学院・医学研究科, 講師 (90260801)
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| Co-Investigator(Kenkyū-buntansha) |
JONO Shuichi Osaka City University, Graduate School of Medicine, Research Associate, 大学院・医学研究科, 助手 (60336790)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2001: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2000: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | interferony / 1.25-dihydroxyvitamin D / macrophages / atherosclerosis / vascular calcification / cytokines / apo E-dehicient mice / vitamin D receptor-deficient mice |
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| Research Abstract |
This project revealed that vitamin D plays an important role in the development of atherosclerotic lesions including plaque calcificatioa. In vitro studies using human monocytfc cell line (THP-1) suggest that the vitamin D activating enzyme, 25-hydroxyvitamin D-1α-hydroxylase can be induced in macrophages infiltrated in atherosclerotic lesions.The coculture studies using human vascular smooth muscle cells (HVSMCs) and THP-1 cells clarified that the calcifying phenotype of smooth muscle cells can be acquired through their interactions with inflammatory cells such as macrophages and T cells in atherosclerotic lesions. Alkaline phosphatase (ALP), one of the pivotal enzymes regulating calcification, was found in the calcified lesions in mouse and rabbit models of atherosclerosis.Furthermore, it was clarified that tumor necrosis factor-α and oncostatin M derived from macrophages may be involved in acquisition of calcifying capacity of smooth muscle cells. Most importantly, stimulation of OSM production by 1,25-dihydroxyvitamin D_3 suggests that vitamin D may play an important role in the atherosclerotic lesions including plaque calcification through the action of OSM. Additionally, the induction of ALP in HVSMCs may be mediated by the actions of NF-_κB and _P38 MAP Finally, apoE- and vitamin D receptor-deficiert mice studies confirmed that the effect of vitamin D may contribute to progression of atherosclerosis.
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