| Project/Area Number |
10218205
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | FIRST DEPARTMENT OF PATHOLOGY, MIYAZAKI MEDICAL COLLEGE |
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Principal Investigator |
ASADA Yujiro (2000-2002) Miyazaki Medical College, First Department of Pathology, professor, 医学部, 教授 (70202588)
住吉 昭信 (1998-1999) 宮崎医科大学, 医学部, 教授 (80038695)
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| Co-Investigator(Kenkyū-buntansha) |
HATAKEYAMA Kinta Research associate, 医学部, 助手 (60325735)
MARUTSUKA Kousuke Research associate, 医学部, 助手 (00239154)
SUMIYOSHI Akinobu Vice-chairman, 医学部, 副学長 (80038695)
木佐貫 篤 宮崎医科大学, 医学部, 助手 (70253846)
浅田 祐士郎 宮崎医科大学, 医学部, 助教授 (70202588)
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| Project Period (FY) |
1998 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥40,500,000 (Direct Cost: ¥40,500,000)
Fiscal Year 2002: ¥6,300,000 (Direct Cost: ¥6,300,000)
Fiscal Year 2001: ¥6,300,000 (Direct Cost: ¥6,300,000)
Fiscal Year 2000: ¥9,900,000 (Direct Cost: ¥9,900,000)
Fiscal Year 1999: ¥8,600,000 (Direct Cost: ¥8,600,000)
Fiscal Year 1998: ¥9,400,000 (Direct Cost: ¥9,400,000)
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| Keywords | adrenomedullin / immunohistochemical localization / atherosclerosis / anticoagulation / mucosal defense / 新規生理活性 / 感染防御 / 血液凝固・線溶 / 免疫組織科学 / 生理活性 / 中耳蝸牛機能 / 血液凝固系 / 心筋梗塞モデル / 心筋保護 / 抗菌作用 / アドレノメデュリン(AM) / PAMP / ヒト生体内分布 / 消化管粘膜 / 培養ヒト内皮細胞 / 血液凝固・線溶系 / 免疫組織学 / ヒト培養内皮細胞 / 組織因子 / 外因系経路阻害因子 |
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| Research Abstract |
AM is widely distributed in human tissues, especially in cardiovascular and endocrine tissues. In the vessels, AM is immunohistochemically present in the vascular smooth muscle cells (SMCs) and endothelial cells (Ecs). In the atherosclerotic lesions, the peptide is present not only in these cells, but also in macrophages, and the most intense AM immunoreactivity is detected in macrophages located in the shoulder lesion of atheromatous plaque, considered to be a rupture prone region. AM inhibits tissue factor production, and AM augments production and release of tissue factor pathway inhibitor from aortic ECs. AM also induced release of antithrombin and urokinase-type plasminogen activator from ECs. Taken together, these antithrombotic properties of the peptide would play an important role in the maintenance of blood circulation. Furthermore, AM immunoreactivity is observed in mucosal and glandular epithelia of the gastrointestinal, respiratory and reproductive systems. AM and proadrenomedullin N-terminal 20 peptide (PAMP) showed a strong antibacterial activity against E. coli. In addition, AM is also present in the auditory system.. These lines of evidence suggest that AM and its related peptides not only play a role in vasodilatation, but also exhibit multiple biological activities in mammals.
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