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Approach to mechanism for post-operative pulmonary vein stenosis: experimental trials for adventitial hemorrhage-associated oxidative stress regulation

Research Project

Project/Area Number 26670190
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Experimental pathology
Research InstitutionThe University of Tokushima

Principal Investigator

SAKASHITA Naomi  徳島大学, 大学院医歯薬学研究部, 教授 (90284752)

Co-Investigator(Kenkyū-buntansha) HORIGUCHI Hidehisa  徳島大学, 大学院医歯薬学研究部, 准教授 (40304505)
NISHITSUJI Kazuchika  徳島大学, 大学院医歯薬学研究部, 助教 (40532768)
Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywordsヘムオキシゲナーゼ1 / 平滑筋 / 酸化ストレス / マクロファージ / 粥状動脈硬化 / 内膜肥厚 / 血管平滑筋 / 術後性肺静脈狭窄症 / 内膜増殖
Outline of Final Research Achievements

We examined neointimal proliferation under situation of hemeoxygenase-1 (HO-1) insufficiency. Smooth muscle cell with hemin treatment showed oxidative stress, temporal overexpression of ERK, NF-κB, STAT3, HO-1 and smooth muscle cell proliferation/migration. Immunohistochemistry revealed strong immunoreactivity of oxidative stress marker, 8OHDG, to the proliferated neointima of the post-operative stenosed pulmonary vein. However, no HO-1 was detected in pulmonary vein. These data suggest that HO-1 expression in pulmonary vein prevented hemin-induced oxidative stress and smooth muscle proliferation. To address this hypothesis, effect of HO-1 inhibitor ZnPP on hemin-induced smooth muscle proliferation was examined but ZnPP exerted no effect on smooth muscle cells proliferation. Because our hypothesis did not confirmed, we next examined role of HO-1 on atherosclerosis. We found foamy transformed macrophages in atheromatous plaque failed to express HO-1 and may promote plaque rupture.

Report

(3 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • Research Products

    (26 results)

All 2016 2015 2014

All Journal Article (9 results) (of which Peer Reviewed: 9 results,  Acknowledgement Compliant: 3 results,  Open Access: 3 results) Presentation (17 results) (of which Invited: 1 results)

  • [Journal Article] The polyphenol (-)-epigallocatechin-3-gallate prevents apoA-IIowa amyloidosis in vitro and protects human embryonic kidney 293 cells against amyloid cytotoxicity.2016

    • Author(s)
      Nakajima H, Nishitsuji K, Kuwabara K, Kawashima H, Uchimura K, Akaji K, Kashiwada Y, Saito H, Sakashita N
    • Journal Title

      Amyloid

      Volume: -

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] CUL2-mediated clearance of misfolded TDP-43 is paradoxically affected by VHL in oligodendrocytes in ALS.2016

    • Author(s)
      Uchida T, Tamaki Y, Ayaki T, Shodai A, Kaji S, Morimura T, Banno Y, Nishitsuji K, Sakashita N, Maki T, Yamashita H, Ito H, Takahashi R, Urushitani M.
    • Journal Title

      Scientific Reports

      Volume: 6 Issue: 1 Pages: 19118-19136

    • DOI

      10.1038/srep19118

    • NAID

      120005689210

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Enthalpy-driven interactions with sulfated glycosaminoglycans promote cell membrane penetration of arginine peptides.2016

    • Author(s)
      Takechi-Haraya Y, Nadai R, Kimura H, Nishitsuji K, Uchimura K, Sakai-Kato K, Ka-wakami K, Shigenaga A, Kawakami T, Otaka A, Hojo H, Sakashita N, Saito H
    • Journal Title

      Biochimica et Biophysica Acta

      Volume: - Issue: 6 Pages: 1339-1349

    • DOI

      10.1016/j.bbamem.2016.03.021

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] CD44-expressing undifferentiated carcinoma with rhabdoid features of the pancreas: molecular analysis of aggressive invasion and metastasis.2015

    • Author(s)
      Ohtomo T, Yoshitani N, Nishitsuji K, Takayama T, Yagagisawa Y, Takeya M, Sakashita N
    • Journal Title

      Pathology International

      Volume: 65 Issue: 5 Pages: 264-270

    • DOI

      10.1111/pin.12283

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] K604, a specific acyl-CoA:CoA:cholesterol acyltransferase 1 inhibitor, suppresses proliferation of U251-MG glioblastoma cells2015

    • Author(s)
      Ohmoto, Takuji Nishitsuji, Kazuchika Yoshitani, Nobuyuki Mizuguchi, Makoto Yanagisawa, Yuto Saito, Hiroyuki Sakashita, Naomi
    • Journal Title

      Molecular Medicine Reports

      Volume: 12 Issue: 4 Pages: 6037-6042

    • DOI

      10.3892/mmr.2015.4200

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Specific ayl-CoA:cholesterol acyltransferase inhibitor, K604, suppresses U251-MG glio-blastoma cells proliferation. in press2015

    • Author(s)
      Ohmoto T, Nishitsuji K, Yoshitani N, Mizuguchi M, Yanagisawa Y, Saito S, Sakashita N
    • Journal Title

      Molecular Medicine Reports

      Volume: 12

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] ACAT1-associated Late Endosomes/Lysosomes Significantly Improve Impaired Intracellular Cholesterol Metabolism and the Survival of Niemann-Pick Type C Mice2014

    • Author(s)
      Kamikawa M, Lei XF, Fujiwara Y, Nishitsuji K, Mizuta H, Takeya M, Sakashita N
    • Journal Title

      ACTA HISTOCHEMICA ET CYTOCHEMICA

      Volume: 47 Issue: 2 Pages: 35-43

    • DOI

      10.1267/ahc.13033

    • NAID

      130003390848

    • ISSN
      0044-5991, 1347-5800
    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Role of ACAT1-positive late endosomes in macrophages: Cholesterol metabolism and therapeutic applications for Niemann-Pick disease type C.2014

    • Author(s)
      Sakashita N, Lei XF, Kamikawa M, Nishitsuji K
    • Journal Title

      Journal of Medical Investigation

      Volume: 61 Pages: 270-277

    • NAID

      130004822731

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Concomitant accumulation of α-synuclein and TDP-43 in a patient with corticobasal degeneration.2014

    • Author(s)
      Yamashita S, Sakashita N, Yamashita T, Tawara N, Tasaki M, Kawakami K, Komohara Y, Fujiwara Y, Kamikawa M, Nakagawa T, Hirano T, Maeda Y, Hasegawa M, Takeya M, Ando Y
    • Journal Title

      Journal of Neurology

      Volume: 261 Issue: 11 Pages: 2209-2217

    • DOI

      10.1007/s00415-014-7491-8

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] AApoA-Iアミロイドーシスにおけるオートファジー・リソソーム系の役割。2015

    • Author(s)
      亀山泰和、西辻和親、小林典裕、斎藤博幸、坂下直実
    • Organizer
      日本病理学会第61回秋期特別総会
    • Place of Presentation
      東京大学、東京都文京区
    • Year and Date
      2015-11-05
    • Related Report
      2015 Annual Research Report
  • [Presentation] AApoAIアミロイドーシスにおけるヘパラン硫酸多硫酸化ドメインの役割。2015

    • Author(s)
      桑原香織、西辻和親、山下太郎、小林典裕、内村健治、安東由喜雄、斎藤博幸、坂下直実
    • Organizer
      第3回アミロイドーシス研究会
    • Place of Presentation
      KKRホテル東京、東京都千代田区
    • Year and Date
      2015-08-21
    • Related Report
      2015 Annual Research Report
  • [Presentation] 肝移植後に著明なステロイド関連心筋肥大を呈した家族性アミロイドポリニューロパチーの症例解析。2015

    • Author(s)
      坂下直実、山下太郎、中川雄伸、安東由喜雄、竹屋元裕
    • Organizer
      第3回アミロイドーシス研究会
    • Place of Presentation
      KKRホテル東京、東京都千代田区
    • Year and Date
      2015-08-21
    • Related Report
      2015 Annual Research Report
  • [Presentation] 肺病変。2015

    • Author(s)
      吉谷信幸、中川雄伸、菰原義弘、竹屋元裕、坂下直実
    • Organizer
      第117回中国四国スライドカンファレンス
    • Place of Presentation
      鳥取大学医学部、米子市、鳥取県
    • Year and Date
      2015-06-27
    • Related Report
      2015 Annual Research Report
  • [Presentation] ApoA-Iアミロイドの毒性に対するヘパラン硫酸糖鎖の影響2015

    • Author(s)
      西辻和親、桑原香織、小林典裕、内村健治、坂下直実、斎藤博幸
    • Organizer
      膜学会第37年会
    • Place of Presentation
      早稲田大学、東京都新宿区
    • Year and Date
      2015-05-14 – 2015-05-15
    • Related Report
      2014 Research-status Report
  • [Presentation] ApoA-Iアミロイドの毒性に対するヘパラン硫酸糖鎖の影響。2015

    • Author(s)
      西辻和親、桑原香織、小林典裕、内村健治、坂下直実、斎藤博幸
    • Organizer
      膜学会37年会
    • Place of Presentation
      早稲田大学、東京都新宿区
    • Year and Date
      2015-05-14
    • Related Report
      2015 Annual Research Report
  • [Presentation] ApoAIアミロイドの毒性に対するヘパラン硫酸の影響。2015

    • Author(s)
      桑原香織、西辻和親、小林典裕、内村健治、斎藤博幸、坂下直実
    • Organizer
      第104回日本病理学会総会
    • Place of Presentation
      名古屋国際会議場、愛知県、名古屋市
    • Year and Date
      2015-04-30 – 2015-05-02
    • Related Report
      2014 Research-status Report
  • [Presentation] ACAT1陽性後期エンドゾーム陽性腫瘍(ACAT1+/CD44+高悪性度腫瘍)はACAT酵素活性依存性に増殖する2015

    • Author(s)
      坂下直実、大本卓司、吉谷信幸、中須千春、柳澤悠登、西辻和親
    • Organizer
      第104回日本病理学会総会
    • Place of Presentation
      名古屋国際会議場、愛知県、名古屋市
    • Year and Date
      2015-04-30 – 2015-05-02
    • Related Report
      2014 Research-status Report
  • [Presentation] ACAT1陽性後期エンドゾーム陽性腫瘍(ACAT1+/CD44+高悪性度腫瘍)はACAT酵素活性依存性に増殖する。2015

    • Author(s)
      坂下直実、大本卓司、吉谷信幸、中須千春、柳澤悠登、西辻和親
    • Organizer
      第104回日本病理学会総会
    • Place of Presentation
      名古屋国際会議場、愛知県、名古屋市
    • Year and Date
      2015-04-30
    • Related Report
      2015 Annual Research Report
  • [Presentation] apoA1アミロイドの毒性に対するヘパラン硫酸糖鎖の影響。2015

    • Author(s)
      桑原香織、西辻和親、小林典裕、内村健治、斎藤博幸、坂下直実
    • Organizer
      第104回日本病理学会総会
    • Place of Presentation
      名古屋国際会議場、愛知県、名古屋市
    • Year and Date
      2015-04-30
    • Related Report
      2015 Annual Research Report
  • [Presentation] ApoAIアミロイドの毒性に対するヘパラン硫酸の影響。2014

    • Author(s)
      桑原香織、西辻和親、小林典裕、内村健治、坂下直実、斎藤博幸
    • Organizer
      第36回生体膜と薬物の相互作用シンポジウム
    • Place of Presentation
      徳島大学医学部、徳島県、徳島市
    • Year and Date
      2014-11-20 – 2014-11-21
    • Related Report
      2014 Research-status Report
  • [Presentation] ApoAIアミロイドの毒性に対するヘパラン硫酸の影響。2014

    • Author(s)
      桑原香織、西辻和親、小林典裕、内村健治、堀口英久、坂下直実、斎藤博幸
    • Organizer
      第2回日本アミロイドーシス研究会学術集会
    • Place of Presentation
      KKRホテル東京、東京千代田区
    • Year and Date
      2014-08-22
    • Related Report
      2014 Research-status Report
  • [Presentation] 血管外膜出血誘発性血管リモデリングの分子病理学的解析:内膜肥厚形成におけるHeme Oxygenase 1の意義。2014

    • Author(s)
      佐藤綾、小浪裕幸、西辻和親、堀口英久、坂下直実
    • Organizer
      第46回日本動脈硬化学会総会
    • Place of Presentation
      京王プラザホテル、東京都新宿区
    • Year and Date
      2014-07-10 – 2014-07-11
    • Related Report
      2014 Research-status Report
  • [Presentation] 代謝制御細胞としてのマクロファージ:粥状動脈硬化、異物貪食、C型Niemann-Pick病、外膜出血誘発性内膜狭窄。2014

    • Author(s)
      坂下直実
    • Organizer
      第54回日本リンパ網内系学会総会
    • Place of Presentation
      山形国際ホテル、山形県、山形市
    • Year and Date
      2014-06-19 – 2014-06-21
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] 頸部皮下腫瘍。2014

    • Author(s)
      中須千春、堀口英久、坂下直実
    • Organizer
      第114回中国四国スライドカンファレンス
    • Place of Presentation
      高知大学医学部、高知県、南国市
    • Year and Date
      2014-06-14
    • Related Report
      2014 Research-status Report
  • [Presentation] ラブドイド分化を示す膵未分化癌の症例解析:悪性形質獲得の分子病態とコレステロール代謝制御療法の可能性。2014

    • Author(s)
      大本卓司、吉谷信幸、堀口英久、坂下直実
    • Organizer
      第103回日本病理学会総会
    • Place of Presentation
      広島国際会議場、広島県、広島市
    • Year and Date
      2014-04-24 – 2014-04-26
    • Related Report
      2014 Research-status Report
  • [Presentation] 血管外膜出血誘発性血管リモデリングの分子病理学的解析:内膜肥厚形成におけるHeme Oxygenase 1の意義。2014

    • Author(s)
      佐藤綾、小浪裕幸、西辻和親、堀口英久、坂下直実
    • Organizer
      第103回日本病理学会総会
    • Place of Presentation
      広島国際会議場、広島県、広島市
    • Year and Date
      2014-04-24 – 2014-04-26
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2017-05-10  

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