| Project/Area Number |
61480205
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
NUMANO Fujio Tokyo Medical and Dental University, 歯学部, 助教授 (40013958)
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| Co-Investigator(Kenkyū-buntansha) |
SHIMOKADO Kentaro Tokyo Medical and Dental University, 歯学部, 助手 (30192115)
KISHI Yukio Tokyo Medical and Dental University, 歯学部, 助手 (70186211)
NISHIYAMA Keiji Tokyo Medical and Dental University, 歯学部, 助手 (00133108)
YAJIMA Michiyoshi Tokyo Medical and Dental University, 歯学部, 講師 (40134671)
沼野 藤江 東京医科歯科大学, 医学部, 助手 (80092427)
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| Project Period (FY) |
1986 – 1987
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| Project Status |
Completed (Fiscal Year 1987)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 1987: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1986: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | vascular injury / atherogenesis / platelets / macrophages / モノクローナル抗体 / 静脈硬化 / 動脈硬化 / 動脈硬化の成因 / 内皮細胞障害 / 血小板の役割 / マクロファージの役割 / モノクローナル抗平滑筋抗体 / モノクローナル抗マクロファージ抗体 / プロスタノイド |
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| Research Abstract |
*recent studies on atherogenesis has been focussed in the roles of platelets (Plt) and macrophages (M<phi>) in the initiation of atherosclerosis. We investigated i)whether or not Plts cause vascular injury and ii)what roles M<phi> play on stenotic changes in venous graft.
1) Roles of platelets in the initiation of atherosclerosis
(A) In vivo study
Healthy male rabbits were used. Serotonin 100<micrn>/kg, TXA_2 (PGH_2 25<micrn>g+ platelet microsome 4mg), STA_2 (l<micrn>g/kg) or platelets (6 x 10(^8)) activated by collagen were flushed in fifteen healthy rabbits. Histological exam showed varying degrees of edematous changes in the intima and media of the coronary artery and aorta.
(B) In vitro study
Confluent vascular endothelial and smooth muscle cells grown in culture dish were used. Addition of activated platelets to the media resulted in damage to the cultured cells dose- and time- dependently as estimated by ]^3H[adenine release. Although TXA_2, STA_2 and serotonin caused dosedependent da
… More
mage to the cells, pdgf had no effects, up to the concentration of 200ng/ml.
2) Roles of M<phi> in the atherosclerotic changes in venous graft
We have performed immunocytochemical investigations of smooth muscle cells and macrophages in atherosclerotic lesions in the femoral vein graft for 4-30 weeks in cholesterol-fed and control rabbits, using monoclonal antibodies specific for muscle cells (RAMll) and macrophages (HHF35; Am. J. Pathol. 126:51, 1987). Most of the lesions were characterized by diffuse intimal thickening consisting mainly of smooth muscle cells. Scattered macrophages were observed in early stages of intimal lesions and macrophage-derived foam cells were observed in medial layer and/or in adventitia, that is, outside of the internal elastic lamina in comparison with the atherosclerotic lesions in aortic wall which were characterized with the accumulation of macrophage-originated foamy cells. These studies demonstrate the nature of the atherosclerotic lesions in the vein graft which resulted from the different structures from those in the arterial wall. Less
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