{"created":"2023-05-15T09:59:01.543726+00:00","id":3102,"links":{},"metadata":{"_buckets":{"deposit":"05e6ad02-c216-4ed1-bca6-de8ab9bb7a27"},"_deposit":{"created_by":5,"id":"3102","owner":"5","owners":[5],"pid":{"revision_id":0,"type":"depid","value":"3102"},"status":"published"},"_oai":{"id":"oai:miyazaki-u.repo.nii.ac.jp:00003102","sets":["72","72:40"]},"author_link":["7741"],"item_10007_description_13":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"ADAMTS-13は、血栓形成を抑制する作用や血小板粘着凝集の抑制を介した内皮細胞の活性化防止作用を有していると考えられ、動脈硬化の進展や急性冠症候群(ACS)の発症に関与していると予想される。本研究においては、ACS患者から採取した検体を用いてADAMTS13を検討し、またIn vitroおよび動物実験により血栓形成に対する作用を検討した。方法:(1)急性心筋梗塞患者の冠動脈から吸引採取された新鮮血栓におけるvon Willebrand factor(VWF)とADAMTS13の局在を、免疫組織化学的手法を用いて検討した。(2)コラーゲンを固層化したガラス板上に、蛍光標識した血小板を含む全血を灌流し、共焦点顕微鏡によるイメージング後、形成された血栓の面積を計測した。(3)動脈硬化性血栓の形成におけるADAMTS-13の役割を検討するために、家兎大腿動脈バルーン再傷害モデルを用いて検討した。結果:(1)ADAMTS13は全ての冠動脈血栓に存在し、VWFとほぼ一致して局在した。(2)コラーゲン上に形成された血栓においても、ADAMTS13はVWFとほぼ一致して存在した。またADAMTS13活性阻害抗体により、灌流6分後の1500/Sにおける血栓面積率と血栓長径は有意に増大した。一方、100/Sずり速度下では、血栓面積率、血栓長径に有意な差を認めなかった。灌流により高分子量のVWFマルチマーは減少したが、ADAMTS13阻害抗体はこれを抑制した。 (3)ADAMTS13活性阻害抗体の投与により、肥厚内膜の傷害15分後に形成される血栓の面積は有意に増大した。考察:ADAMTS13は血栓内に存在し、高壁ずり速度下においてVWF切断を介して動脈硬化性血栓の形成を抑制することが示唆された。したがって、ACS発症に対しても深く関与していると考えられた。","subitem_description_language":"ja","subitem_description_type":"Abstract"},{"subitem_description":"Background : Disruption of atherosclerotic plaque with subsequent thrombus formation is a major cause of atherothrombosis. Von Willebrand factor (VWF), ultra-large multimers of which are cleaved by ADAMTS-13, plays a important role in thrombus formation. However, the role of ADAMTS-13 during thrombogenesis remains unknown. Methods and Results : We studied the localization of ADAMTS-13 in fresh coronary thrombi obtained from patients with acute myocardial infarction (AMI). We also examined the roles of ADAMTS-13 in thrombus formation using collagen-coated flow chambers (100S-1 and 1,500S-1) and on injured neointima of rabbit femoral arteries. ADAMTS-13 was detected in thrombi of AMI and in the flow chamber, where it colocalized with VWF. The surface area covered by platelet adhesion and the long axes of platelet thrombi were higher under 1,500S^-1 than under 100S^-1 of shear rate, and both the area and long axes were significantly augmented with an antibody to the ADAMTS-13 disintegrin-like domain (WH2-22-1A), but not to the thrombospondin 1-3 domain (WH10) under 1,500S^-1 of shear rate. WH2-22-1A, but not WH10, reduced the activity of plasma ADAMTS-13 to cleave large VWF multimers during perfusion. Reducing ADAMTS-13 activity with WH2-22-1A also resulted in the significant augmentation of thrombus formation on injured neointima of rabbit femoral arteries in vivo. Conclusion : These clinical, in vitro human blood, and in vivo animal experiments suggest the role of disintegrin-like domain of ADAMTS-13 in down-regulating the thrombus growth on diseased arteries under high shear rate conditions.","subitem_description_type":"Abstract"}]},"item_10007_description_14":{"attribute_name":"内容記述","attribute_value_mlt":[{"subitem_description":"平成18年度~平成19年度 科学研究費補助金 \n(基盤研究(C)) \n研究成果報告書","subitem_description_language":"ja","subitem_description_type":"Other"}]},"item_10007_textarea_26":{"attribute_name":"目次情報","attribute_value_mlt":[{"subitem_textarea_language":"ja","subitem_textarea_value":"目次\n1.研究発表\n学会誌など(投稿論文)・・・・・・・・・・pp.4-6\n原著論文\n総説\n学会発表(口頭発表そのほか)・・・・pp.7-9\nシンポジウム\n国際学会\n国内学会(一般公演)\n2.研究成果・・・・pp.10\n研究目的\n研究成果の概要\n3.投稿論文別冊\n(原著論文)\n1)Tsuruda, T., Kato, J., Hatakeyama, K., Yamashita, A., Nakamura, K., Imamura, T., et al. (2006). Adrenomedullin in mast cells of abdominal aortic aneurysm. Cardiovascular Research, 70(1), 158-164.\nhttp://dx.doi.org/10.1016/j.cardiores.2006.02.003\n2)Yamashita, A., Sumi, T., Goto, S., Hoshiba, Y., Nishihira, K., Kawamoto, R., et al. (2006). Detection of von willebrand factor and tissue factor in platelets-fibrin rich coronary thrombi in acute myocardial infarction. American Journal of Cardiology, 97(1), 26-28.\nhttp://dx.doi.org/10.1016/j.amjcard.2005.07.105\n3)Hoshiba, Y., Hatakeyama, K., Tanabe, T., Asada, Y., & Goto, S. (2006). Co-localization of von willebrand factor with platelet thrombi, tissue factor and platelets with fibrin, and consistent presence of inflammatory cells in coronary thrombi obtained by an aspiration device from patients with acute myocardial infarction. Journal of Thrombosis and Haemostasis, 4(1), 114-120.\nhttp://dx.doi.org/10.1111/j.1538-7836.2005.01701.x\n4)Nishihira, K., Imamura, T., Yamashita, A., Hatakeyama, K., Shibata, Y., Nagatomo, Y., et al. (2006). Increased expression of interleukin-10 in unstable plaque obtained by directional coronary atherectomy. European Heart Journal, 27(14), 1685-1689.\nhttp://dx.doi.org/10.1093/eurheartj/ehl058\n5)Kawamoto, R., Yamashita, A., Nishihira, K., Furukoji, E., Hatakeyama, K., Ishikawa, T., et al. (2006). Different inflammatory response and oxidative stress in neointimal hyperplasia after balloon angioplasty and stent implantation in cholesterol-fed rabbits. Pathology Research and Practice, 202(6), 447-456.\nhttp://dx.doi.org/10.1016/j.prp.2005.12.011\n6)Liang, J., Liu, E., Yu, Y., Kitajima, S., Koike, T., Jin, Y., et al. (2006). Macrophage metalloelastase accelerates the progression of atherosclerosis in transgenic rabbits. Circulation, 113(16), 1993-2001.\nhttp://dx.doi.org/10.1161/CIRCULATIONAHA.105.596031\n7)Fujita, S., Nagamachi, S., Nishii, R., Wakamatsu, H., Futami, S., Tamura, S., et al. (2006). Relationship between cancer cell proliferation, tumour angiogenesis and 201Tl uptake in non-small cell lung cancer. Nuclear Medicine Communications, 27(12), 989-997.\nhttp://dx.doi.org/10.1097/01.mnm.0000243371.26507.3c\n8)Yamasaki, M., Fujita, S., Ishiyama, E., Mukai, A., Madhyastha, H., Sakakibara, Y., et al. (2007). Soy-derived isoflavones inhibit the growth of adult T-cell leukemia cells in vitro and in vivo. Cancer Science, 98(11), 1740-1746.\nhttp://dx.doi.org/10.1111/j.1349-7006.2007.00595.x\n9)Takajo, I., Umeki, K., Morishita, K., Yamamoto, I., Kubuki, Y., Hatakeyama, K., et al. (2007). Engraftment of peripheral blood mononuclear cells from human T-lymphotropic virus type 1 carriers in NOD/SCID/γcnull (NOG) mice. International Journal of Cancer, 121(10), 2205-2211.\nhttp://dx.doi.org/10.1002/ijc.22972\n10)Hamuro, T., Kido, H., Asada, Y., Hatakeyama, K., Okumura, Y., Kunori, Y., et al. (2007). Tissue factor pathway inhibitor is highly susceptible to chymase-mediated proteolysis. FEBS Journal, 274(12), 3065-3077.\nhttp://dx.doi.org/10.1111/j.1742-4658.2007.05833.x\n11)Myoishi, M., Hao, H., Minamino, T., Watanabe, K., Nishihira, K., Hatakeyama, K., et al. (2007). Increased endoplasmic reticulum stress in atherosclerotic plaques associated with acute coronary syndrome. Circulation, 116(11), 1226-1233.\nhttp://dx.doi.org/10.1161/CIRCULATIONAHA.106.682054\n12)Nishihira, K., Imamura, T., Hatakeyama, K., Yamashita, A., Shibata, Y., Date, H., et al. (2007). Expression of interleukin-18 in coronary plaque obtained by atherectomy from patients with stable and unstable angina. Thrombosis Research, 121(2), 275-279.\nhttp://dx.doi.org/10.1016/j.thromres.2007.04.003\n(総説)\n1)畠山金太､浅田祐士郎 : 病理学的立場から内皮機能改善と心筋梗塞発症予防を探る. Vascular Medicine 2 : 36-42, 2006\n2)畠山金太､浅田祐士郎 : 冠動脈血栓の成り立ち. Coronary Intervention 2 : 10-16, 2006\n3)鶴田敏博､畠山金太､浅田祐士郎 : 動脈硬化の血管基盤; 血管外膜. 循環器科 59(suppl. 3) : 39-48, 2006\n4)畠山金太､浅田祐士郎 : 不安定プラークの病理. Vascular Lab 4 : 366-372, 2007\n5)畠山金太､浅田祐士郎 : プラークの病理. 医学のあゆみ 221 : 1141-1145, 2007\n6)畠山金太､浅田祐士郎 : 冠動脈の閉塞性血栓の形成における血栓と炎症の関連を探る. Vascular Medicine 3 : 295-301, 2007\n7)畠山金太､浅田祐士郎 : アテローム血栓症における炎症性因子の関与. 内分泌･糖尿病科 24 : 298-303, 2007\n8)山下篤､佐藤勇一郎､畠山金太､浅田祐士郎 : 心､脳､末梢血管イベントにおけるリスクの違いを極める; 解剖学的違いからみる. Vascular Medicine 3 : 99-105, 2007"}]},"item_10007_version_type_20":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_970fb48d4fbd8a85","subitem_version_type":"VoR"}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2020-06-21"}],"displaytype":"detail","filename":"666kaken.pdf","filesize":[{"value":"431.3 kB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"666kaken.pdf","url":"https://miyazaki-u.repo.nii.ac.jp/record/3102/files/666kaken.pdf"},"version_id":"05745268-9f7c-41d6-b7f7-7fe05a4e8ea7"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"急性冠症候群, 共焦点顕微鏡, 免疫染色, 組織病理学, 血栓イメージング, 冠動脈吸引血栓","subitem_subject_language":"ja","subitem_subject_scheme":"Other"},{"subitem_subject":"Immunohistochemistry, ADAMTS-13, Atherothroinhosis, Von Willebrand factor, Acute myocardial infarction, Histopathology, Flow chamber, rabbit femoral artery","subitem_subject_language":"en","subitem_subject_scheme":"Other"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"jpn"}]},"item_researcher":{"attribute_name":"研究代表者","attribute_type":"creator","attribute_value_mlt":[{"creatorNames":[{"creatorName":"畠山, 金太","creatorNameLang":"ja"},{"creatorName":"ハタケヤマ, キンタ","creatorNameLang":"ja-Kana"}],"nameIdentifiers":[{}]}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"research report","resourceuri":"http://purl.org/coar/resource_type/c_18ws"}]},"item_title":"急性冠症候群の発症におけるADAMTS-13の関与","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"急性冠症候群の発症におけるADAMTS-13の関与","subitem_title_language":"ja"},{"subitem_title":"Involvement of ADAMTS-13 in the pathogenesis of acute coronary syndrome","subitem_title_language":"en"}]},"item_type_id":"10007","owner":"5","path":["72","40"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2012-11-08"},"publish_date":"2012-11-08","publish_status":"0","recid":"3102","relation_version_is_last":true,"title":["急性冠症候群の発症におけるADAMTS-13の関与"],"weko_creator_id":"5","weko_shared_id":-1},"updated":"2024-01-30T04:25:07.304122+00:00"}