Pathophysiological significance of the factor which enhances the action of oxidized LDL, platelets, and leukocytes on vascular wall.

2012 Fiscal Year Final Research Report

• Project/Area Number: 22390051
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General pharmacology
• Research Institution: National Cardiovascular Center Research Institute
• Principal Investigator: SAWAMURA Tatsuya 独立行政法人国立循環器病研究センター, 研究所, 部長 (30243033)
• Project Period (FY): 2010 – 2012
• Keywords: 酸化 / LDL / LOX-1 / 血小板 / 血栓

Research Abstract

We have identified a co-factor which enhances the binding of oxidized LDL and platelets to LOX-1, an oxidized LDL receptor, promoting blood coagulating reaction in LOX-1 dependent manner. The interaction between LOX-1 and the co-factor might be a key reaction to determine the onset and progression of atherothrombotic diseases.

Research Products

• [Journal Article] Davidge, S.T. and Kenny, L.C. : Lectin-like oxidized low-density lipoprotein l(LOX-l) receptor inhibition protects against pre-elamspsia plasma mediated vascular dysfunction. (2013)
  • Author(s): English, F.A., McCarthy, F.P., McSweeney, C.L., Quon, A.L., Morton, J.S., Sawamura, T.
  • Journal Title: Am J Hypertens Volume: 26 Pages: 279-286
  • DOI: doi:10.1093/ajh/hps035
• [Journal Article] Small dense low-density lipoproteins cholesterol can predict incident cardiovascular disease in an urban Japanese cohort : The Suita study. (2013)
  • Author(s): Arai, H., Kokubo, Y., Watanabe, M., Sawamura, T., Ito, Y., Minagawa, A., Okamura, T. and Miyamato, Y.
  • Journal Title: J Atheroscler Thromb Volume: 20 Pages: 195-203
  • DOI: doi:10.5551/jat.14936
• [Journal Article] Dietary cholesterol oxidation products accelerate plaque destabilization and rupture associated with monocyte infiltration/activation via the MCP-1-CCR2 pathway in mouse brachiocephalic arteries : Therapeutic effects of ezetimibe. (2012)
  • Author(s): Sato, K., Nakano, K., Katsuki, S., Matoba, T., Osada, K., Sawamura, T., Sunagawa, K. and Egashira, K.
  • Journal Title: J Atheroscler Thromb Volume: 19 Pages: 986-998
  • DOI: doi:10.5551/jat.13391
• [Journal Article] Lectin-like oxidized low-density lipoprotein 1 receptor in a reduced uteroplacental perfusion pressure rat model of preeclampsia. (2012)
  • Author(s): Morton, J.S., Abdalvand, A., Jiang, Y., Sawamura, T., Uwiera, R.R. and Davidge, S.T.
  • Journal Title: Hypertension Volume: 59 Pages: 1014-1020
  • DOI: doi:10.1161/HYPERTENSIONAHA.112.191825
• [Journal Article] Lectin-like oxidized low-density lipoprotein receptor 1 signal is a potent biomarker and therapeutic target for human rheumatoid arthritis. (2012)
  • Author(s): Ishikawa, M., Ito, H., Akiyoshi, M., Kume, N., Yoshitomi, H., Mitsuoka, H., Tanida, S., Murata, K., Shibuya, H., Kasahara, T., Kakino, A., Fujita, Y., Sawamura, T., Yasuda, T. and Nakamura, T.
  • Journal Title: Arthritis Rheum Volume: 64 Pages: 1024-1034
  • DOI: doi:10.1002/art.33452
• [Journal Article] Lectin-like oxidized LDL receptor 1 is involved in CRP-mediated complement activation. (2011)
  • Author(s): Fujita, Y., Yamaguchi, S., Kakino, A., Iwamoto, S., Yoshimoto, R. and Sawamura, T.
  • Journal Title: Clin Chem Volume: 57 Pages: 1398-1405
  • DOI: doi:10.1373/clinchem.2011.168625
• [Journal Article] An alternative protein standard to measure activity of LOX-1 ligand containing apoB (LAB)-utilization of anti-LOX-1 single- chain antibody fused to apoB fragment. (2011)
  • Author(s): Iwamoto, S., Fujita, Y., Kakino, A., Yanagida, K., Matsuda, H., Yoshimoto, R. and Sawamura, T.
  • Journal Title: J Atheroscler Thromb Volume: 18 Pages: 818-828
  • DOI: doi:10.5551/jat.9142
• [Journal Article] LOX-1 deletion improves neutrophil responses, enhances bacterial clearance, and reduces lung injury in a murine polymicrobial sepsis model. (2011)
  • Author(s): Wu, Z., Sawamura, T., Kurdowska, A.K., Ji, H.L., Idell, S. and Fu, J.
  • Journal Title: Infect Immun Volume: 79 Pages: 2865-2870
  • DOI: doi:10.1128/IAI.01317-10
• [Journal Article] Associations of atherosclerotic risk factors with oxidized low-density lipoprotein evaluated by LOX-1 ligand activity in healthy men. (2011)
  • Author(s): Uchida, K., Suehiro, A., Nakanishi, M., Sawamura, T. and Wakabayashi, I.
  • Journal Title: Clin Chim Acta Volume: 412 Pages: 1643-1647
  • DOI: doi:10.1016/j.cca.2011.05.022
• [Journal Article] Procyanidins are potent inhibitors of LOX-1 : a new player in the French Paradox. (2011)
  • Author(s): Nishizuka, T., Fujita, Y., Sato, Y., Nakano, A., Kakino, A., Ohshima, S., Kanda, T., Yoshimoto, R. and Sawamura, T.
  • Journal Title: Proc Jpn Acad Ser B Phys Biol Sci Volume: 87 Pages: 104-113
  • DOI: doi:10.2183/pjab.87.104
• [Journal Article] LOX index, a novel predictive biochemical marker for coronary heart disease and stroke. (2010)
  • Author(s): Inoue, N., Okamura, T., Kokubo, Y., Fujita, Y., Sato, Y., Nakanishi, M., Yanagida, K., Kakino, A., Iwamoto, S., Watanabe, M., Ogura, S., Otsui, K., Matsuda, H., Uchida, K., Yoshimoto, R. and Sawamura, T.
  • Journal Title: Clin Chem Volume: 56 Pages: 550-558
  • DOI: doi:10.1373/clinchem.2009.140707
• [Journal Article] Pitavastatin reduces lectin-like oxidized low-density lipoprotein receptor-1 ligands in hypercholesterolemic humans. (2010)
  • Author(s): Matsumoto, T., Fujita, M., Sawamura, T., Kakino, A., Sato, Y., Fujita, Y., Matsuda, H., Nakanishi, M., Uchida, K., Nakae, I., Kanda, H., Yoshida, A., Miwa, K., Hayashi, H., Mitsunami, K. and Horie, M.
  • Journal Title: Lipids Volume: 45 Pages: 329-335
  • DOI: doi:10.1007/s11745-010-3402-7
• [Presentation] Measurement and manipulation of lox-1 ligand level to predict and to prevent (2012)
  • Author(s): Tatsuva Sawamura
  • Organizer: 17th World Congress on Heart Disease
  • Place of Presentation: カナダ
  • Year and Date: 20120727-30
• [Presentation] LOX-1研究を支えてくれた人と言葉 (2012)
  • Author(s): 沢村達也
  • Organizer: 第44回日本動脈硬化学会総会・学術集会
  • Place of Presentation: 福岡
  • Year and Date: 20120719-20
• [Presentation] Identification of an endogenous inhibitor to block the interaction between oxLDL and its receptors (2012)
  • Author(s): Akemi Kakino, Yoshiko Fujita, Tomohide Takaya, Shin Iwamoto, Tatsuya Sawamura
  • Organizer: 第44回日本動脈硬化学会総会・学術集会
  • Place of Presentation: 福岡
  • Year and Date: 20120719-20
• [Presentation] Serum level of LOX-1 ligand containing apoB (LAB) was associated with an increased risk of subclinical atherosclerosis in us white and Japanese men (2012)
  • Author(s): Okamura, T., Sekikawa, A., Sawamura, T., Kadowaki,T., Kim Sutton-Tyrrell, Daniel Edmundowicz, Murakami, Y., Miura, K., Lewis H Kuller,Ueshima,H.
  • Organizer: XVI International Symposium on Atherosclerosis
  • Place of Presentation: シドニー
  • Year and Date: 20120325-29
• [Presentation] An endogenous oxidized LDL inhibitor Del-1 (2012)
  • Author(s): Akemi Kakino, Yoshiko Fujita, Tomohide Takaya, Shin Iwamoto, Tatsuya Sawamura
  • Organizer: XVI International Symposium on Atherosclerosis
  • Place of Presentation: シドニー
  • Year and Date: 20120325-29
• [Presentation] Identification of Del-1 as an endogenous oxidized LDL inhibitor (2012)
  • Author(s): 垣野明美、藤田佳子、高谷智英、岩元真、沢村達也
  • Organizer: 第85回日本薬理学会年会
  • Place of Presentation: 京都
  • Year and Date: 20120314-16
• [Presentation] 内因性酸化LDL阻害分子の同定 (2012)
  • Author(s): 垣野明美、藤田佳子、高谷智英、岩元真、沢村達也
  • Organizer: 第8回宮崎サイエンスキャンプ
  • Place of Presentation: 宮崎
  • Year and Date: 20120217-19
• [Presentation] LOX-1とそのリガンドを標的とした心血管病の診断・予防・治療の試み (2012)
  • Author(s): 沢村達也
  • Organizer: 関西広域バイオメディカルクラスター成果発表
  • Place of Presentation: 大阪
  • Year and Date: 20120131-021
• [Presentation] 変性LDLの考え方 (2012)
  • Author(s): 沢村達也
  • Organizer: 地域イノベーション戦略支援プログラム神戸トライアルに関する研究者会議
  • Place of Presentation: 神戸
  • Year and Date: 2012-12-13
• [Presentation] 酸化LDL受容体LOX-1の機能を通してわかってきた心血管機能不全のメカニズム (2012)
  • Author(s): 沢村達也
  • Organizer: 私立大学戦略的研究基盤形成支援事業・薬学総合研究所サイエンスフォーラム心血管系の老化と疾患に対する研究戦略
  • Place of Presentation: 大阪
  • Year and Date: 2012-10-27
• [Presentation] 心血管機能におけるLOX-1の意義とその診断治療への応用 (2012)
  • Author(s): 沢村達也
  • Organizer: 第4回酸化LDL勉強会
  • Place of Presentation: 香川
  • Year and Date: 2012-09-28
• [Presentation] 多機能受容体LOX-1の循環器疾患における役割 (2012)
  • Author(s): 沢村達也
  • Organizer: 明海大学第350回研修会(第219回大学院総合セミナー共催)
  • Place of Presentation: 埼玉
  • Year and Date: 2012-09-21
• [Presentation] ヒト核内受容体PPARαによる生体防御レクチンMBL2の発現制御機構の解析 (2012)
  • Author(s): 橘敬祐、竹内健太郎、稲田大彦、杉本研、石本憲司、田中十志也、楽木宏実、浜窪隆雄、酒井寿郎、児玉龍彦、沢村達也、土井健史
  • Organizer: 第121回日本薬理学会近畿部会
  • Place of Presentation: 徳島
  • Year and Date: 2012-06-29
• [Presentation] 十年後の脳閉塞を予測する～新規バイオマーカー『LOX-index』～ (2012)
  • Author(s): 沢村達也
  • Organizer: 第12回日本抗加齢医学会総会イブニングセミナー
  • Place of Presentation: 横浜
  • Year and Date: 2012-06-23
• [Presentation] 酸化LDL受容体LOX-1の研究からわかったこと (2012)
  • Author(s): 沢村達也
  • Organizer: 静岡県立大学薬学月例セミナー
  • Year and Date: 2012-06-11
• [Presentation] 循環器臨床研究の今後の展望について (2012)
  • Author(s): 沢村達也
  • Organizer: 21世紀の循環器医療を考える会
  • Place of Presentation: 京都
  • Year and Date: 2012-05-25
• [Presentation] 天然物から見出したLOX-1アンタゴニスト・プロシアニジンはSHRSP血管壁への脂質沈着を抑制する (2011)
  • Author(s): 垣野明美、西塚太一、藤田佳子、佐藤優子、中野厚史、善本亮、沢村達也
  • Organizer: 第15回日本心血管内分泌代謝学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 20111125-26
• [Presentation] 心不全における左室LOX-1の発現量と可溶型LOX-1の血中濃度は心機能を反映する (2011)
  • Author(s): 高谷智英、和田啓道、藤田佳子、森本達也、長谷川浩二、沢村達也
  • Organizer: 第15回日本心血管内分泌代謝学会学術総会
  • Place of Presentation: 大阪
  • Year and Date: 20111125-26
• [Presentation] 超高齢化社会への処方隻一酸化LDL受容体研究からの展望 (2011)
  • Author(s): 沢村達也
  • Organizer: Bio Japan 2011
  • Place of Presentation: 横浜
  • Year and Date: 20111005-07
• [Presentation] 高血圧性心不全モデルラットにおける左室LOX-1の発現量は心機能と相関する (2011)
  • Author(s): 高谷智英、和田啓道、藤田佳子、森本達也、長谷川浩二、沢村達也
  • Organizer: 第47回高血圧関連疾患モデル学会学術総会
  • Place of Presentation: 札幌
  • Year and Date: 20110906-07
• [Presentation] Implication of small dense LDL as a risk for coronary artery disease in a urban Japanese cohort : The Suita study (2011)
  • Author(s): Hidenori Arai, Yoshihiko Kokubo, Makoto Watanabe, Yoshihiro Miyamoto, Tatsuya Sawamura. Tomonori Okamura
  • Organizer: 第43回日本動脈硬化学会総会・学術集会
  • Place of Presentation: 札幌
  • Year and Date: 20110714-16
• [Presentation] Contribution of LOX-1 in the aortic aneurysm and effects of PI polyamide targeting LOX-1 (2011)
  • Author(s): Ayako Takasaka, Noboru Fukuda, Takahiro Ueno, Akiko Tunemi, Yoshiaki Kusumi, Yukihiko Orime, Motomi Shiono, Tatsuya Sawamura
  • Organizer: 第43回日本動脈硬化学会総会・学術集会
  • Place of Presentation: 札幌
  • Year and Date: 20110714-16
• [Presentation] Procyanindin inhibits oxidized LDL binding to LOX-1 and suppresses vascular lipid accumulation in SHRSP rats (2011)
  • Author(s): Ryo Yoshimoto, Taichi Nshizuka, Yoshiko Fujita, Yuko Sato, Atsushi Nakano, Shunji Ohshima, Tomomasa Kanda, Tatsuya Sawamura
  • Organizer: 第43回日本動脈硬化学会総会・学術集会
  • Place of Presentation: 札幌
  • Year and Date: 20110714-16
• [Presentation] プロシアニジンはLOX-1アンタゴニストであり、血管壁への脂質沈着を抑制する (2011)
  • Author(s): 善本亮、西塚太一、藤田佳子、佐藤優子、中野厚史、垣野明美、大嶋俊二、神田智正、沢村達也
  • Organizer: 第84回日本薬理学会
  • Place of Presentation: 横浜
  • Year and Date: 20110322-24
• [Presentation] 心不全Dahlラットの心機能低下に伴い左室LOX-1の発現は亢進する (2011)
  • Author(s): 高谷智英、和田啓道、藤田佳子、森本達也、沢村達也、長谷川浩二
  • Organizer: 第21回日本循環薬理学会
  • Place of Presentation: 岡山
  • Year and Date: 2011-12-02
• [Presentation] 血管機能における変性LDL受容体LOX-1研究の新しい展開 (2011)
  • Author(s): 沢村達也
  • Organizer: 第4回最新動脈硬化フォーラム
  • Place of Presentation: 大阪
  • Year and Date: 2011-11-04
• [Presentation] 酸化LDL測定のための人工標準蛋白作製 (2010)
  • Author(s): 岩元真、藤田佳子、垣野明美、柳田一樹、善本亮、沢村達也
  • Organizer: 第83回日本生化学会大会、第33回日本分子生物学会年会
  • Place of Presentation: 神戸
  • Year and Date: 20101207-10
• [Presentation] プロシアニジンは酸化LDL受容体LOX-1のアンタゴニストであり、ラット血管壁への脂質沈着を抑制する (2010)
  • Author(s): 西塚太一、藤田佳子、佐藤優子、中野厚史、垣野明美、大嶋俊二、神田智正、善本亮、沢村達也
  • Organizer: 第20回日本循環薬理学会
  • Place of Presentation: 札幌
  • Year and Date: 20101111-12
• [Presentation] C-Reactive protein binds to LOX-1 and causes vascular dysfunction via complement activation (2010)
  • Author(s): Fujita, Y., Otsui, K., Kakino, A.,Yamaguchi, S.,Sato, Y., Yoshimoto, R., SawamuraX
  • Organizer: 第14回国際SHRシンポジウム
  • Place of Presentation: モントリオール
  • Year and Date: 20100922-27
• [Presentation] LOX-1 is involved in the complement activation by endogenous C-Reactive protein and myocardial reperfusion injury (2010)
  • Author(s): Fujita, Y., Otsui, K., Kakino, A.,Yamaguchi, S., Sato,Y., Yoshimoto, R.,Sawamura,T.
  • Organizer: 15th World Cogress on Heart Disease
  • Place of Presentation: バンクーバー
  • Year and Date: 20100724-28
• [Presentation] LOX-1 in cardiovascular dysfunction (2010)
  • Author(s): Sawamura.T.
  • Organizer: 15th World Cogress on Heart Disease
  • Place of Presentation: バンクーバー
  • Year and Date: 20100724-28
• [Presentation] The effect of LOX-1 and LOX-1 ligands containing ApoB on the incidence of coronary heart disease and stroke in an 11-year population-based cohort study: The Suita study (2010)
  • Author(s): Okamura, T., Inoue, N., Kokubo, Y, Fujita, Y, Sato, Y., Watanabe, M。Sawamura,T.
  • Organizer: 第42回日本動脈硬化学会
  • Place of Presentation: 岐阜
  • Year and Date: 20100715-16
• [Presentation] LOχ-l,the oxidized LDL receptor, in cardiovascular dysfunction (2010)
  • Author(s): 沢村達也
  • Organizer: Basic Research Seminar at Texas Heart Institute
  • Place of Presentation: ヒューストン
  • Year and Date: 20100531-0602
• [Presentation] LOX-1 in cardiovascular dysfunction (2010)
  • Author(s): Sawamura, T.
  • Organizer: New Frontier in Diagnosis and Management of CV Diseases in 2010
  • Place of Presentation: タイチェン
  • Year and Date: 2010-11-21
• [Presentation] SHR-SPの血管壁脂質沈着におけるLOX-1の役割 (2010)
  • Author(s): 沢村達也
  • Organizer: 第13回Vitamin E Update Forum
  • Place of Presentation: 東京
  • Year and Date: 2010-08-20
• [Presentation] 酸化LDL受容体LOX-1と心血管病 (2010)
  • Author(s): 沢村達也
  • Organizer: 第3回臨床研究フォーラム
  • Place of Presentation: 静岡
  • Year and Date: 2010-08-06
• [Presentation] CRP in LOX-1 Biology (2010)
  • Author(s): 沢村達也
  • Organizer: Workshop on C-Reactive Protein
  • Place of Presentation: バーミンガム
  • Year and Date: 2010-06-03
• [Presentation] Recognition of endogenous C-reactive protein by LOX-1 abrogates myocardial infarction (2010)
  • Author(s): 藤田佳子,垣野明美,佐藤優子,善本亮,沢村達也
  • Organizer: ISHR World Corgress 2010
  • Place of Presentation: 京都
  • Year and Date: 2010-05-13
• [Remarks]
  • URL: http://www.ncvc.go.jp/res/divisions/vascular_physiology/index.html
• [Patent(Industrial Property Rights)] 酸化LDL阻害剤 (2013)
  • Inventor(s): 沢村達也、垣野明美
  • Industrial Property Rights Holder: 国立循環器病研究センター
  • Industrial Property Number: PCT/JP2013/52929
  • Filing Date: 2013-02-07
  • Overseas
• [Patent(Industrial Property Rights)] 酸化LDL阻害剤 (2012)
  • Inventor(s): 沢村達也、垣野明美
  • Industrial Property Rights Holder: 国立循環器病研究センター
  • Industrial Property Number: 特願2012-027793
  • Filing Date: 2012-02-10
• [Patent(Industrial Property Rights)] 融合タンパク質、核酸、ベクター、細胞、LABの測定方法、並びに、LAB測定用キット (2010)
  • Inventor(s): 沢村達也、岩元真
  • Industrial Property Rights Holder: 国立循環器病研究センター、(株)バイオマーカーサイエンス
  • Industrial Property Number: 特願2010-251701,特開2012-100585
  • Filing Date: 2010-11-10