Elucidation of molecular mechanism of plaque destabilization and identification of predictable factors for acute coronary syndrome

2012 Fiscal Year Final Research Report

• Project/Area Number: 22390159
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: The University of Tokushima
• Principal Investigator: SATA Masataka 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 教授 (80345214)
• Co-Investigator(Kenkyū-buntansha): SOEKI Takeshi 徳島大学, 大学院・ヘルスバイオサイエンス研究部, 教授 (60393211) ; HIRATA Yasunobu 東京大学, 医学部附属病院, 特任准教授 (70167609)
• Project Period (FY): 2010 – 2012
• Keywords: 動脈硬化 / 血管新生 / 慢性炎症 / HMGB-1 / 急性冠症候群プラーク破裂

Research Abstract

We tried to elucidate molecular mechanism of plaque destabilization by analyzing clinical samples and utilizing animal models. The concentration of HMGB1, a non-histone nuclear protein, increased at coronary sinus in patients with coronary artery disease. Particularly, acute coronary syndrome, such as acute myocardial infarction or unstable angina pectoris, was associated with ten times elevated HMGB1 level. Animal experiments revealed that HMGB1-DNA complex signal contributed destabilization of vessel wall by activating Toll-like receptor 9 in the bone marrow-derived cells.

Research Products

• [Journal Article] eneficial effect of a synthetic prostacyclin agonist, ONO-1301, in rat autoimmune myocarditis mode (2013)
  • Author(s): Hirata Y, Kurobe H, Uematsu E, Yagi S, Soeki T, Yamada H, Fukuda D, Shimabukuro M, Nakayama M, Matsumoto K, Sakai Y, Kitagawa T,Sata M
  • Journal Title: Eur J Pharmacol Volume: 699 Pages: 81-87
  • DOI: doi:10.1016/j.ejphar.2012.11.045
  • Peer Reviewed
• [Journal Article] Exendin-4, a glucagon-like peptide-1 receptor agonist, attenuates neointimal hyperplasia after vascular injury (2013)
  • Author(s): Hirata Y, Kurobe H, Nishio C, Tanaka K, Fukuda D, Uematsu E, Nishimoto S, Soeki T, Harada N, Sakaue H, Kitagawa T, Shimabukuro M, Nakaya N, Sata M
  • Journal Title: Eur J Pharmacol Volume: 699 Pages: 106-111
  • DOI: doi:10.1016/j.ejphar.2012.11.057
  • Peer Reviewed
• [Journal Article] Ulcer-like projection caused by a penetrating branch to the bronchial artery. (2013)
  • Author(s): Ise T, Fujioka K, Iwase T, Hotchi J, Akaike M, Sata M.
  • Journal Title: J Am Coll Cardiol. Volume: 61 Pages: e147.
  • DOI: doi:10.1016/j.jacc.2012.10.047
  • Peer Reviewed
• [Journal Article] Constrictive pericarditis with intrapericardial abscess. (2013)
  • Author(s): H, Ogasawara K, Bando S, Ise T, Niki T, Kusunose K, Ueda Y, Tomita N, Yamaguchi K, Taketani Y, Iwase T, Soeki T, Wakatsuki T, Horiguchi H, Sakashita N, Sata M
  • Journal Title: Circ J. Volume: 77 Pages: 786-788
  • DOI: doi:10.1253/circj.CJ-12-1098
  • Peer Reviewed
• [Journal Article] Perivascular adipose tissue-secreted angiopoietin-like protein2 (Angptl2) accelerates neointimal hyperplasia after endovascular injury. (2013)
  • Author(s): Tian Z, Miyata K, Tazume H, Sakauguchi H, Kadomatsu T, Horio E, Takahashi O, Komohara Y, Araki K, Hirata Y, Tabata M, Takanashi S, Takeya M, Hao H, Shimabukuro M, Sata M, Kawasuji M, Oike Y.
  • Journal Title: J Mol Cell Cardiol Volume: 57 Pages: 1-12.
  • DOI: doi:10.1016/j.yjmcc.2013.01.004
  • Peer Reviewed
• [Journal Article] Interval from the Onset of Transmitral Flow to Annular Velocity Is a Marker of LV Filling Pressure. (2013)
  • Author(s): Kusunose K, Yamada H, Nishio S, Tomita N, Niki T, Yamaguchi K, Taketani Y, Iwase T, Soeki T, Wakatsuki T, Sata M
  • Journal Title: JACC Cardiovasc Imaging. Volume: 6 Pages: 528-530
  • DOI: doi:10.1016/j.jcmg.2012.10.025
  • Peer Reviewed
• [Journal Article] Epicardial adipose tissue volume and adipocytokine imbalance are strongly linked to human coronary atherosclerosis. (2013)
  • Author(s): Shimabukuro M, Hirata Y, Tabata M, Dagvasumberel M, Sato H, Kurobe H, Fukuda D, Soeki T, Kitagawa T, Takanashi S, Sata M.
  • Journal Title: Arterioscler Thromb Vasc Biol Volume: 33 Pages: 1077-1084
  • DOI: doi:10.1161/ATVBAHA.112.300829
  • Peer Reviewed
• [Journal Article] Aliskiren in combination with valsartan exerts synergistic protective effects against ventricular remodeling after myocardial infarction in mice (2012)
  • Author(s): Higashikuni Y, Takaoka M, Iwata H, Tanaka K, Hirata Y, Nagai Y, Sata M.
  • Journal Title: Hypertens Re Volume: 35 Pages: 62-69
  • DOI: doi:10.1038/hr.2011.136
  • Peer Reviewed
• [Journal Article] A synthetic prostacyclin agonist thrombozane synthase inhibitory activity, ONO-1301, protects myocardium from ischemia/reperfusion injury. (2012)
  • Author(s): Hirata Y, Shimabukuro M, Uematsu E, Soeki T, Yamada H, Sakai Y, Nakamura M, Matsumoto K, Igarashi T, Sata M
  • Journal Title: Eur J Pharmacol. Volume: 674 Pages: 352-358.
  • DOI: doi:10.1016/j.ejphar.2011.10.038
  • Peer Reviewed
• [Journal Article] The ATP-binding cassette transporter ABCG2 protects against pressure overload-induced cardiac hypertrophy and heart failure by promoting angiogenesis and antioxidant response (2012)
  • Author(s): Higashikuni Y, Sainz J, Nakamura K, Takaoka M, Enomoto S, Iwata H, Kimie T, Sahara M, Hirata Y, Nagai R, Sata M.
  • Journal Title: Arterioscler Thromb Vasc Biol Volume: 32 Pages: 654-661
  • DOI: doi:10.1161/ATVBAHA.111.240341
  • Peer Reviewed
• [Journal Article] Nicorandil attenuates monocrotaline-induced vascular endothelial damage and pulmonary arterial hypertension. (2012)
  • Author(s): Sahara M, Sata M, Morita T, Hirata Y, Nagai R
  • Journal Title: PLoS One Volume: 7 Pages: e33367.
  • DOI: doi:10.1371/journal.pone.0033367
  • Peer Reviewed
• [Journal Article] The Radioprotective 105/MD-1 complex contributes to diet-induced obesity and adipose tissue inflammation. (2012)
  • Author(s): Watanabe Y, Nakamura T, Ishikawa S, Fujisaka S, Usui I, Tsuneyama K, Ichihara Y, Wada T, Hirata Y, Suganami T, Izaki H, Akira S, Miyake K, Kanayama H, Shimabukuro M, Sata M, Sasaoka T, Ogawa Y, Tobe K, Takatsu K, Nagai Y
  • Journal Title: Diabetes. Volume: 61 Pages: 1199-1209.
  • DOI: doi:10.2337/db11-1182
  • Peer Reviewed
• [Journal Article] Activation of AMPK-Sirt1 pathway by telmisartan in white adipose tissue: A possible link to anti-metabolic effects (2012)
  • Author(s): Shiota A, Shimabukuro M, Fukuda D, Soeki T, Sato H, Uematsu E, Hirata Y, Kurobe H, Sakaue H, Nakaya Y, Masuzaki H, Sata M
  • Journal Title: Eur J Pharmacol Volume: 692 Pages: 84-90
  • DOI: doi:10.1016/j.ejphar.2012.07.026
  • Peer Reviewed
• [Journal Article] Telmisartan ameliorates insulin sensitivity by activating the AMPK/SIRT1 pathway in skeletal muscle of obese db/db mice (2012)
  • Author(s): Shiota A, Shimabukuro M, Fukuda D, Soeki T, Sato H, Uematsu E, Hirata Y, Kurobe H, Maeda N, Sakaue H, Masuzaki H, Shimomura I, Sata M.
  • Journal Title: Cardiovascular Diabetol. Volume: 11 Pages: 139.
  • DOI: doi:10.1186/1475-2840-11-139
  • Peer Reviewed
• [Journal Article] Index-beat Assessment of Left Ventricular Systolic and Diastolic Function during Atrial Fibrillation using Myocardial Strain and Strain Rate (2012)
  • Author(s): Kusunose K, Yamada H, Nishio S, Tomita N, Hotchi J, Bando M, Niki T, Yamaguchi K, Taketani Y, Iwase T, Soeki T, Wakatsuki T, Sata M.
  • Journal Title: J Am Soc Echocardiogr Volume: 25 Pages: 953-959
  • DOI: doi:10.1016/j.echo.2012.06.009
  • Peer Reviewed
• [Journal Article] Renoprotective and antioxidant effects of cilnidipine in hypertensive patients. (2012)
  • Author(s): Soeki T, Kitani M, Kusunose K, Yagi S, Taketani Y, Koshiba K, Wakatsuki T, Orino S, Kawano K, Sata M
  • Journal Title: Hypertens Res. Volume: 35 Pages: 1058-1062
  • DOI: doi:10.1038/hr.2012.9
  • Peer Reviewed
• [Journal Article] Reciprocal expression of MRTF-A and myocardin is crucial for pathological vascular remodelling in mice (2012)
  • Author(s): Minami T, Kuwahara K, Nakagawa Y, Takaoka M, Kinoshita H, Nakao K, Kuwabara Y, Yamada Y, Yamada C, Shibata J, Usami S, Yasuno S, Nishikimi T, Ueshima K, Sata M, Nakano H, Seno T, Kawahito Y, Sobue K, Kimura A, Nagai R, Nakao K
  • Journal Title: EMBO J Volume: 31 Pages: 4428-4440
  • DOI: doi:10.1038/emboj.2012.296.
  • Peer Reviewed
• [Journal Article] Local persistent hypercoagulability after sirolimus-eluting stent implantation in patients with stable angina. (2011)
  • Author(s): Yamaguchi K, Wakatsuki T, Niki T, Kusunose K, Koshiba K, Yagi S, Taketani Y, Iwase T, Tomita N, Yamada H, Soeki T, Akaike M, Sata M
  • Journal Title: Int J Cardiol. Volume: 153 Pages: 272-276
  • DOI: doi:10.1016/j.ijcard.2010.08.014
  • Peer Reviewed
• [Journal Article] Comparison of chronic-stage histopathological findings among 3 coronary stents implanted in the same patient. (2011)
  • Author(s): Niki T, Wakatsuki T, Yamaguchi K, Kusunose K, Koshiba K, Yagi S, Taketani Y, Iwase T, Tomita N, Yamada H, Soeki T, Akaike M, Sata M
  • Journal Title: Int J Cardiol. Volume: 150 Pages: e25-e27
  • DOI: doi:10.1016/j.ijcard.2009.08.032
  • Peer Reviewed
• [Journal Article] Coronary atherosclerosis is associated with macrophage polarization in epicardial adipose tissue (2011)
  • Author(s): Hirata Y, Tabata M, Kurobe H, Motoki T, Akaike M, Nishio C, Higashida M, Mikasa H, Nakaya Y, Takanashi S, Igarashi T, Kitagawa T, Sata M
  • Journal Title: J Am Coll Cardiol Volume: 58 Pages: 248-255
  • DOI: doi:10.1016/j.jacc.2011.01.048
  • Peer Reviewed
• [Journal Article] Pre-clinical data on the role of mineralocorticoid receptor antagonists in reversing vascular inflammatio (2011)
  • Author(s): Yagi S, Sata M.
  • Journal Title: Eur Heart J Suppl Volume: 13 Pages: B15-B20
  • DOI: doi:10.1093/eurheartj/sur012
  • Peer Reviewed
• [Journal Article] Effect of low-dose (1 mg/day) pitavastatin on left ventricular diastolic function and albuminuria in patients with hyperlipidemia. (2011)
  • Author(s): Yagi S, Akaike M, Aihara KI, Iwase T, Ishikawa K, Yoshida S, Sumitomo-Ueda Y, Kusunose K, Niki T, Yamaguchi K, Koshiba K, Taketani Y, Tomita N, Yamada H, Soeki T, Wakatsuki T, Matsumoto T, Sata M.
  • Journal Title: Am J Cardiol Volume: 107 Pages: 1644-1649
  • DOI: doi:10.1016/j.amjcard.2011.01.054
  • Peer Reviewed
• [Journal Article] Enhanced inflammation in epicardial fat in patients with coronary artery disease (2011)
  • Author(s): Hirata Y, Kurobe H, Akaike M, Chikugo F, Hori T, Bando Y, Nishio C, Higashida M, Nakaya Y, Kitagawa T, Sata M.
  • Journal Title: Int Heart J Volume: 52 Pages: 139-142.
  • DOI: doi:10.1536/ihj.52.139
  • Peer Reviewed
• [Journal Article] Serial imaging changes during treatment of Takayasu arteritis with pulmonary artery stenosis (2011)
  • Author(s): Kusunose K, Yamada H, Tomita N, Nishio S, Niki T, Yamaguchi K, Koshiba K, Yagi S, Taketani Y, Iwase T, Soeki T, Wakatsuki T, Akaike M, Sata M.
  • Journal Title: Int J Cardiol. Volume: 148 Pages: e47-e50
  • DOI: doi:10.1016/j.ijcard.2009.02.036
  • Peer Reviewed
• [Journal Article] Increased expression of macrophage-inducible C-type lectin in adipose tissue of obese mice and humans (2011)
  • Author(s): Ichioka M, Suganami T, Tsuda N, Shirakawa I, Hirata Y, Satoh-Asahara N, Shimoda Y, Tanaka M, Kim-Saijo M, Miyamoto Y, Kamei Y, Sata M, Ogawa Y.
  • Journal Title: Diabetes. Volume: 60 Pages: 819-826
  • DOI: doi:10.2337/db10-0864
  • Peer Reviewed
• [Journal Article] Acute hemodynamic effects of adaptive servo ventilation in patients with pulmonary hypertension (2011)
  • Author(s): Yagi S, Akaike M, Iwase T, Kusunose K, Niki T, Yamaguchi K, Koshiba K, Taketani Y, Tomita N, Yamada H, Soeki T, Wakatsuki T, Sata M
  • Journal Title: Int J Cardiol. Volume: 148 Pages: 125-127
  • DOI: doi:10.1016/j.ijcard.2011.01.074
  • Peer Reviewed
• [Journal Article] Bosentan improves systemic sclerosis-related peripheral circulation insufficiency. (2011)
  • Author(s): Yagi S, Akaike M, Aihara KI, Iwase T, Sumitomo-Ueda Y, Yoshida S, Matsumoto T, Sata M.
  • Journal Title: Int J Cardiol. Volume: 147 Pages: 472-47
  • DOI: doi:10.1016/j.ijcard.2011.01.0
  • Peer Reviewed
• [Journal Article] Augmented angiogenesis in adventitia promotes growth of atherosclerotic plaque in apolipoprotein E-deficient mice. (2011)
  • Author(s): Tanaka K, Nagata D, Hirata Y, Tabata Y, Nagai R, Sata M.
  • Journal Title: Atherosclerosis. Volume: 215 Pages: 366-373
  • DOI: doi:10.1016/j.atherosclerosis.2011.01.016
  • Peer Reviewed
• [Journal Article] High plasma aldosterone concentration is a novel risk factor of cognitive impairment in patients with hypertension (2011)
  • Author(s): Yagi S, Akaike M, Aihara KI, Iwase T, Yoshida S, Sumitomo-Ueda Y, Ikeda Y, Ishikawa K, Matsumoto T, Sata M
  • Journal Title: Hypertens Res. Volume: 34 Pages: 74-78
  • DOI: doi:10.1038/hr.2010.179
  • Peer Reviewed
• [Journal Article] Validation of longitudinal peak systolic strain by speckle tracking echocardiography with visual assessment and myocardial perfusion SPECT in patients with regional asynergy (2011)
  • Author(s): Kusunose K, Yamada H, Nishio S, Mizuguchi Y, Choraku M, Maeda Y, Hosokawa S, Yamazaki N, Tomita N, Niki T, Yamaguchi K, Koshiba K, Soeki T, Wakatsuki T, Akaike M, Sata M
  • Journal Title: Circ J. Volume: 75 Pages: 141-147.
  • DOI: doi:10.1253/circj.CJ-10-0551
  • Peer Reviewed
• [Book] 1. 田中君枝、佐田政隆 『5. 動脈硬化とアレルギー・炎症 (2013)
  • Author(s): 田中君枝、佐田政隆
  • Total Pages: 34-40
  • Publisher: 』 Annual Review 循環器 2013(小室一成、佐地勉、坂田隆造、赤阪隆史 編集)中外医学社
• [Book] 4. 治療薬総論 硝酸薬』 今日の循環器疾患治療指針 第3 版(井上博、許俊鋭、檜垣實男、代田浩之、筒井裕之 編 (2013)
  • Author(s): 竹谷善雄、佐田政隆
  • Total Pages: 162-165
  • Publisher: 医学書院
• [Book] 2.PPARγ』 動脈硬化症の新しい診断・治療標的(倉林正彦 監修、山岸昌一 編集 (2012)
  • Author(s): 田中君枝、佐田政隆
  • Total Pages: 75-82
  • Publisher: メディカルレビュー社
• [Book] 6. 不安定プラーク破裂に関与する因子は何か? (2012)
  • Author(s): 山口浩司、佐田政隆
  • Total Pages: 26-29
  • Publisher: 中外医学社
• [Book] 南江堂 (2012)
  • Author(s): 島袋充生、佐田政隆
  • Total Pages: 507-510
  • Publisher: 心臓病と肥満-メタボリックシンドロームを中心に-
• [Book] 第II 章 8 トランスレーショナルリサーチに期待する予防医学 (2012)
  • Author(s): 田中君枝、佐田政隆
  • Total Pages: 96-101
  • Publisher: 南山堂
• [Book] 第6 章 病態・治療 Tissue Engineering 技術による血管の再生 (2011)
  • Author(s): 黒部裕嗣、佐田政隆
  • Total Pages: 427-428
  • Publisher: 血管生物医学事典(日本血管生物医学会 編集)朝倉書店
• [Book] 第5章 異所性脂肪と循環器疾患 (2010)
  • Author(s): 平田陽一郎、高岡稔、佐田政隆
  • Total Pages: 79-103
  • Publisher: 日本医事新報社
• [Book] 6 節バルーン傷害モデル (2010)
  • Author(s): 田中君枝、佐田政隆
  • Total Pages: 175-178
  • Publisher: LIFE-SCIENCE INFORMATION CENTER
• [Book] 心膜疾患、腫瘍 4.心内血栓 循環器疾患 最新の治療 (2010)
  • Author(s): 仁木敏之、佐田政隆
  • Total Pages: 213-216
  • Publisher: 南江堂
• [Remarks]
  • URL: http://square.umin.ac.jp/~TOKUSHIM/