| Project/Area Number |
12670709
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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 |
Circulatory organs internal medicine
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| Research Institution | Department of Internal Medicine III Kurume University school of Medicine |
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Principal Investigator |
IKEDA Hisao Department of Internal Medicine III Kurume University school of Medicine, Associate Professor, 医学部, 助教授 (50168134)
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| Co-Investigator(Kenkyū-buntansha) |
MUROHARA Toyoaki Cardiovascular Research Institute Kurume University, Assistant. Professor, 循環器研究所, 講師 (90299503)
大塚 頼隆 久留米大学, 医学部, 助手 (90309774)
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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 |
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2001: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 2000: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | Platelets / Platelet aggregation / Matrix metalloproteinases / Thrombosis / Matrix metalloproteinase inhibitor / 血栓症 / MMP阻害薬 / 血小板 / 生体内血栓形成 / Matrix metalloproteinase / 血小板凝集 / 内皮障害 / 血栓閉塞時間 |
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| Research Abstract |
Plaque rupture and subsequent platelet aggregation play an important role in the disease processes of acute coronary syndromes. Although it have been extensively analysed that degradation of extracellular matrix proteins by matrix metalloproteinases (MMPs) plays an active role in plaque rupture, the role of MMPs in intraarterial thrombus formation is little known. This issue is relevant since a recent study showed that platelets can release MMP-2 and hence contribute to platelet aggregation in vitro (Sawicki et al. Nature 1997). Here we examined the effects of a synthetic MIVIP inhibitor (BB-94) on intraarterial thrombus formation in viva and ox vivo platelet aggregation. Rats given intraperitoneal injection of BB-94 (10 and 30 mg/kg) (low BB and high BB groups, respectively), and control rats given vehicle alone (C group) were subjected to a carotid arterial thrombosis model by means of perivascular FeC13 delivery. Time to thrombotic occlusion (after delivery of FeC13) measured by doppler flow probe was significantly longer in the high BB group (37±7 min) than in the low BB group (242 min) and C group (191 min) (p<0.05, respectively) indicating inhibition of arterial thrombus formation. Collagen induced ox vivo platelet aggregation was significantly lower in the low BB group (19±7 %) and high BB group (17±4 %) than in the C group (44±7 %) (p<0.01, respectively). Immunohistchemical examination revealed that platelet MMP-2 expressions were noted within arterial thrombi, in consistence with location of platelet Pselectin expressions. A synthetic MMP inhibitor, BB-94, inhibits platelet-mediated thrombus formation in arterial thrombosis mOdel, suggesting an important role of MMP-2 in thrombus formation. The inhibition of the MMP function might become a potentially useful therapeutic modality to prevent acute thrombotic disease.
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