Basic Research for Development of Phannacotherapy targeting Cell Adhesion Molecules for Vascular Hyperplasia
| Project/Area Number |
12672217
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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 |
応用薬理学・医療系薬学
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| Research Institution | The University of Tokushima |
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Principal Investigator |
TAKIGUCHI Yoshiharu The University of Tokushima, Graduate School of, Pharmaceutical Sciences, Associate Professor, 薬学研究科, 助教授 (40163349)
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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: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2000: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | Restenosis / Neointimal thickening / Leukocyte / Cell adhesion / P-Selectin / Mac-1 / Vitamin E / Oxidative stress / 血管内膜障害 / 血管リモデリング / 接着分子 / セレクチン |
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| Research Abstract |
The early response to vascular injury is characterized by adhesion of leukocytes capable of releasing various inflammatciy mediators. Leukocytes are proposed to play a role in restenosis after balloon angioplasty. To test the hypothesis, we examined the effect of blockade of cell adhesion molecules, sefectin and Mac-1, on neointimal thickening after balloon injury in normal control and vitamin E-deprived rats mice. An increased accumulation of activated leukocytes and an augmented intimal thickening was observed in the injured artery of vitamin E-deprived animals. Blockade of selectins selections concerned with leukocyte rolling by fucoidin, an inhibitor of L-selection and P-selection, or anti-P-selection antibody significantly attenuated the augmented intimal thickening in vitamin E-deprived animals, but their effects was less in control animals. While blocking firm leukocyte adhesion following rolling by anti-Mac-1 antibody failed to inhibited neointimal involved in the development ofrestenosis in high oxidative stress induced by vitamin E deficiency, which may cause the augmentation of intimal thickening, Recruitment of circulation leukocytes by selection followed by the activation of them, is the more important event in the possible rote of leukocytes. Endogenous vitamin E may have a protective effect against progression of restenosis by modulating leukocyte-dependent responses. Given the limitation of currently available preventive therapy for restenosis, blodking leukocyte recmitment may be an attractive strategy for preventing restenosis in patients with high oxidative state, e.g., hyperlipdemia, diabetes mellitus.
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Report
(3 results)
Research Products
(3 results)
