Investigation to clarify the role of endothelial mesenchymal transition in cardiac fibrosis

• Project/Area Number: 24591113
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Mie University
• Principal Investigator: OKAMOTO Ryuji 三重大学, 医学部附属病院, 講師 (60378346)
• Co-Investigator(Kenkyū-buntansha): ITO Masaaki 三重大学, 大学院医学研究科・循環器内科学, 教授 (00223181)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 心臓線維化 / 心肥大 / 心筋梗塞 / 内皮間葉以降 / レポーターマウス / 線維化 / 高血圧症 / 内皮間葉移行現象 / TGFβ / Rhoキナーゼ

Outline of Final Research Achievements

We assessed the hypothesis that endothelial mesenchymal transition played an important role in cardiac fibrosis. We generated pTie2-Cre and lox-tdTomato double transgenic mouse with a marker for endothelial cell-derived cells and performed the ligation of left coronary artery. Additionally we crossed those mice with pFSP1-EGFP mice. tdTomato expression was recognized specifically in endothelial cells. In cardiac fibrosis some cells expressed both the tdTomato and EGFP. However we could not observe the cells expressing tdTomato and periostin, a fibroblast-specific marker, simultaneously. Therefore we concluded endothelial mesenchymal transition did not play an important role in cardiac fibrosis.

Research Products

• [Journal Article] Resveratrol sensitizes HepG2 cells to TRAIL-induced apoptosis. (2014)
  • Author(s): Tameda M, Sugimoto K, Shiraki K, Inagaki Y, Ogura S, Kasai C, Yoneda M, Okamoto R, Yamamoto N, Takei Y, Ito M, Nobori T.
  • Journal Title: Anticancer Drugs. Volume: 25 Issue: 9 Pages: 1028-1034
  • DOI: 10.1097/cad.0000000000000128
  • Peer Reviewed
• [Journal Article] Collagen triple helix repeat containing 1 is overexpressed in hepatocellular carcinoma and promotes cell proliferation and motility. (2014)
  • Author(s): Tameda M, Sugimoto K, Shiraki K, Yamamoto N, Okamoto R, Usui M, Ito M, Takei Y, Nobori T, Kojima T, Suzuki H, Uchida M, Uchida K.
  • Journal Title: Int J Oncol. Volume: 45 Issue: 2 Pages: 541-548
  • DOI: 10.3892/ijo.2014.2445
  • NAID: 120007136651
  • Peer Reviewed
• [Journal Article] Persistent release of IL-1s from skin is associated with systemic cardio-vascular disease, emaciation and systemic amyloidosis: the potential of anti-IL-1 therapy for systemic inflammatory diseases. (2014)
  • Author(s): Yamanaka K, Nakanishi T, Saito H, Maruyama J, Isoda K, Yokochi A, Imanaka-Yoshida K, Tsuda K, Kakeda M, Okamoto R, Fujita S, Iwakura Y, Suzuki N, Ito M, Maruyama K, Gabazza EC, Yoshida T, Shimaoka M, Mizutani H.
  • Journal Title: PLoS One. Volume: 9 Issue: 8 Pages: 104479-104479
  • DOI: 10.1371/journal.pone.0104479
  • Peer Reviewed / Open Access
• [Journal Article] Effects of cardiac resynchronization therapy on left ventricular mechanical dyssynchrony induced by right ventricular pacing in a patient with heart failure and preserved ejection fraction. (2014)
  • Author(s): Takeuchi T, Dohi K, Kumagai N, Nakamori S, Fujimoto N, Okamoto R, Fujii E, Kitamura T, Yamada N, Nakamura M, Hamada M, Ito M.
  • Journal Title: Int J Cardiol. Volume: 177 Issue: 3 Pages: 1069-1072
  • DOI: 10.1016/j.ijcard.2014.10.083
  • Peer Reviewed
• [Journal Article] Fulminant myocarditis in a patient with severe coronary artery disease (2014)
  • Author(s): Fujita S, Okamoto R, Takamura T, Nakajima H, Tanabe M, Nakamori S, Dohi K, Tanigawa T, Nakamura M, Ito M.
  • Journal Title: Journal of Cardiology Cases Volume: 9 Issue: 1 Pages: 15-17
  • DOI: 10.1016/j.jccase.2013.08.010
  • Peer Reviewed
• [Journal Article] FHL2 prevents cardiac hypertrophy in mice with cardiac-specific deletion of ROCK2. (2013)
  • Author(s): Noma K, Okamoto R, Li Y, Hiroi Y, Liu PY, Taniguchi M, Ito M, Liao JK.
  • Journal Title: FASEB J. Volume: 27 Issue: 4 Pages: 1439-1449
  • DOI: 10.1096/fj.12-217018
  • Peer Reviewed
• [Journal Article] Identification of bovine hibernation-specific protein complex and evidence of its regulation in fasting and aging (2013)
  • Author(s): Fujita, S., Okamoto, R., Taniguchi, M., Ban-Tokuda, T., Konishi, K., Goto, I., Yamamoto, Y., Sugimoto, K., Takamatsu, N., Nakamura, M., Shiraki, K., Buechler, C., Ito, M.
  • Journal Title: J. Biochem Volume: 153巻 Issue: 5 Pages: 453-461
  • DOI: 10.1093/jb/mvt008
  • Peer Reviewed
• [Journal Article] Marked improvement of renal failure and severe hypertension after renal artery stenting in the solitary functioning kidney (2013)
  • Author(s): Sawai T, Miyahara M, Okamoto R, Dohi K, Tanigawa T, Yamada N, Nakamura M, Ito M.
  • Journal Title: Journal of Cardiology Cases Volume: 7 Issue: 3 Pages: e82-e85
  • DOI: 10.1016/j.jccase.2012.12.001
  • Peer Reviewed
• [Journal Article] A case of aortic thrombosis and embolism preceding the progression of early esophageal cancer (2013)
  • Author(s): Goto I, Okamoto R, Sawai T, Takasaki A, Takeuchi T, Matsuo H, Miyahara M, Nakamura M, Ito M.
  • Journal Title: Journal of Cardiology Cases Volume: 7 Issue: 5 Pages: e123-e125
  • DOI: 10.1016/j.jccase.2012.12.008
  • Peer Reviewed
• [Presentation] Endothelial mesenchymal transitions do not contribute to the development of pulmonary arterial hypertension caused by a VEGF receptor inhibitor in mice (2015)
  • Author(s): Ryuji Okamoto, Itaru Goto, Yoshito Ogihara, Norikazu Yamada, Hirokazu Okada and Masaaki Ito
  • Organizer: European Society of Cardiology (ESC) congress
  • Place of Presentation: 英国ロンドン市
  • Year and Date: 2015-08-30
• [Presentation] The Identification of Mutation in ELP2 using Whole Exome Sequence in a Severe Form of Familial Hypertrophic Cardiomyopathy. (2015)
  • Author(s): Ryuji Okamoto, Itaru Goto, Ryotaro Hashizume, Naoshi Shimojo, Kaoru Dohi, Mashio Nakamura and Masaaki Ito.
  • Organizer: 日本循環器学会総会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2015-04-24
• [Presentation] A Familial Hypertrophic Cardiomyopathy is Caused by a Mutation in Elp2, Encoding One of Subunits of Elongator Acetyltransferase Complex (2014)
  • Author(s): Ryuji Okamoto, Itaru Goto, Issei Kobayashi, Ryotaro Hashizume, Naoshi Shimojo, Kaoru Dohi, Mashio Nakamura and Masaaki Ito.
  • Organizer: American Heart Association (AHA) meeting
  • Place of Presentation: 米国シカゴ市
  • Year and Date: 2014-11-17
• [Presentation] A mutation in Elongator Protein 2 can cause a severe form of familial hypertrophic cardiomyopathy (2014)
  • Author(s): Ryuji Okamoto, Itaru Goto, Issei Kobayashi, Naoshi Shimojo, Kaoru Dohi, Mashio Nakamura and Masaaki Ito.
  • Organizer: European Society of Cardiology (ESC) congress
  • Place of Presentation: スペインバルセロナ市
  • Year and Date: 2014-08-31
  • Invited
• [Presentation] 心血管疾患発症進展における遺伝・環境的要因（パネルディスカッション） (2012)
  • Author(s): 岡本隆二
  • Organizer: 第60回日本心臓病学会学術集会
  • Place of Presentation: 石川県立音楽堂
• [Presentation] Identification of Bovine Hibernation-Specific Protein Complex and Evidence of its Regulation in Fasting and Aging (2012)
  • Author(s): 岡本隆二
  • Organizer: 第72回米国糖尿病学会(ADA)
  • Place of Presentation: フィラデルフィア国際会議場
• [Remarks] 三重大学教員紹介 岡本隆二
  • URL: http://kyoin.mie-u.ac.jp/profile/1233.html
• [Remarks] 三重大学全学シーズ集 岡本隆二
  • URL: http://www.crc.mie-u.ac.jp/seeds/contents/detail.php?mid=20100305-110541&t=b
• [Remarks] 三重大学教員紹介 岡本隆二
  • URL: http://kyoin.mie-u.ac.jp/profile/1233.html
• [Remarks] 三重大学全学シーズ集 岡本隆二
  • URL: http://www.crc.mie-u.ac.jp/seeds/contents/detail.php?mid=20100305-110541&t=b