Pathophysiology in platelet-mediated thrombus model
| Project/Area Number |
10670687
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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 | Kurume University |
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Principal Investigator |
IKEDA Hisao School of Medicine, Kurume University Assistant Professor, 医学部, 助教授 (50168134)
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| Co-Investigator(Kenkyū-buntansha) |
ONITSUKA Ichiro School of Medicine, Kurume University Assistant, 医学部, 助手 (10289431)
MUROHARA Toyoaki School of Medicine, Kurume University Lecturer, 循環器研究所, 講師 (90299503)
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| Project Period (FY) |
1998 – 2000
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1998: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | thrombus formation / platelet / leukocyte / endothelial cell / P-selectin / endothelial injuries / monoclonal antibody against P-selectin / Sialyl LewisィイD1xィエD1-containing oligosaccharide / 生体内顕微鏡 / 生体内血栓 / 腸間膜動脈 / 接着分子 / 分子生物学 |
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| Research Abstract |
To pursue the molecular biology regarding pathophysiologic interaction among leukocyte, platelet and endothelial cell, we attempted to make a rat thrombosis model which manifest platelet-mediated cyclic flow variations (CFVs). Mesenteric arteries were dissected free from adherent fat and connective tissue under an intravita1 microscopy- To induce thrombosis, we damaged a short segment of mesenteric artery by compression using a blunted glass micropipette attached to a micromanipulator, and exposed the damaged media to the bloodstream. However, it was difficult to make a rat model as mentioned above. Therefore, we studied the interaction among leukocyte, platelet and endothelial cell using dog model of CFVs. By now cytometric analysis, platelet P-selectin expression was significantly upregulated during the episode of CFVs. Immunohistochemical analysis revealed the incorporation of platelets with upregulated P-selectin within thrombi at the stenotic site. Microscopic observations reveale
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d the presence of numerous platelets adhered to leukocytes at the stenotic site on the damaged endothelium. Sialyl LewisィイD1xィエD1-containing oligosaccharide (SleィイD1xィエD1-OS) significantly reduced CFVs, inhibited platelet P-selectin expression, and prevented the adherence of platelets and leukocytes on the damaged endothelium. H the coronary arteries distal to thrombosis sites, endothelium-dependent relaxation was impaired after observing CFVs for 80 minutes. Electron microscopy revealed the loss of endothelia1 integrity with leukocyte adherence to the endothelium in the distal sites. Immunohistochemical expression of P-selectin on the endothelial cells was more upregulated in the distal sites than in the proximal sites, and P-selectin mRNA expression was significantly greater in the ischemic region distal to the thrombotic site than in the proximal nonischemic region. A neutralizing monoclonal antibody against p-selectin and SleィイD1xィエD1-OS preserved endothelial function without affecting CFVs.-OS preserved endothelial integrity of distal site and inhibited P-selectin expression of the distal site. Thus, present findings suggest that the adhesive interaction between P-selectin and SleィイD1xィエD1 plays and important role not only platelet-mediated thrombus formation but also endothelial injuries of the coronary artery distal to the thrombotic sites. Less
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Report
(3 results)
Research Products
(6 results)
