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Investigation of cyclic mechanical stretch-inducued vasular smooth muscle cell death and the development of prevention strategies of aortic dissection

Research Project

Project/Area Number 26460345
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General pharmacology
Research InstitutionNara Medical University

Principal Investigator

Yoshizumi Masanori  奈良県立医科大学, 医学部, 教授 (60294667)

Co-Investigator(Kenkyū-buntansha) 小澤 健太郎  奈良県立医科大学, 医学部, 准教授 (80507393)
京谷 陽司  奈良県立医科大学, 医学部, 助教 (10706534)
Research Collaborator ZHAO Jing  奈良県立医科大学, 医学部, 博士研究員
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords動脈解離 / 血管平滑筋細胞 / 細胞死 / 伸展負荷 / 分子機構 / ケモカイン / MAPキナーゼ / カルシウム拮抗薬 / アンジオテンシンII受容体拮抗薬
Outline of Final Research Achievements

The pulsatile nature of blood flow exposes vascular smooth muscle cells (VSMCs) in the vessel wall to cyclic mechanical stretch (CMS), which evokes vascular remodeling. We have revealed that CMS of rat aortic smooth muscle cells (RASMCs) caused JNK- and p38-dependent cell death and that a calcium channel blocker and angiotensin II receptor antagonist decreased cell death by CMS. We also showed that the expression of chemokines, Cxcl1 and Cx3cl1 was induced by CMS in a JNK-dependent manner. Expression of Cxcl1 was also induced in VSMCs by hypertension produced by abdominal aortic constriction. In addition, antagonists against the receptors for CXCL1 and CX3CL1 increased cell death, indicating that CXCL1 and CX3CL1 protect RASMCs from CMS-induced cell death. These results indicate that CMS of VSMCs induces inflammation-related gene expression, including that of CXCL1 and CX3CL1, which may play important roles in the stress response against CMS caused by hypertension.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (24 results)

All 2017 2016 2015 2014 Other

All Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 6 results,  Acknowledgement Compliant: 3 results) Presentation (15 results) (of which Invited: 2 results) Remarks (3 results)

  • [Journal Article] Detection of Nitric Oxide Induced by Angiotensin II Receptor Type 1 Using Soluble Guanylate Cyclase beta1 Subunit Fused to a Yellow Fluorescent Protein, Venus2016

    • Author(s)
      Yuichi Tsuji, Kentaro Ozawa, Akira T. Komatsubara, Jing Zhao, Mayumi Nishi, Masanori Yoshizumi
    • Journal Title

      J. Fluoresc.

      Volume: - Issue: 1 Pages: 399-405

    • DOI

      10.1007/s10895-016-1968-z

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Endothelin-1(1-31) causes the migration of vascular smooth muscle cells through endothelin ETA receptor2016

    • Author(s)
      Yoji Kyotani, Jing Zhao, Kentaro Ozawa, Takahiro nakagawa,Francesco A. Bolstad, Masanori Yoshizumi
    • Journal Title

      Brit. J. Pharmaceut. Res.

      Volume: 13 Issue: 6 Pages: 1-7

    • DOI

      10.9734/bjpr/2016/29824

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Exendin-4 Prevents Vascular Smooth Muscle Cell Proliferation and Migration by Angiotensin II via the Inhibition of ERK1/2 and JNK Signaling Pathways2015

    • Author(s)
      Kosuke Nagayama, Yoji Kyotani, Jing Zhao, Satoyasu Ito, Kentaro Ozawa, Francesco A. Bolstad, Masanori Yoshizumi
    • Journal Title

      Plos One

      Volume: 10 Issue: 9 Pages: e0137960-e0137960

    • DOI

      10.1371/journal.pone.0137960

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Angiotensin (1-7), Small But Complicated, Needs More Exercise2015

    • Author(s)
      Masao Yoshizumi, Masanori Yoshizumi
    • Journal Title

      Circulation Journal

      Volume: 79 Issue: 6 Pages: 1220-1221

    • DOI

      10.1253/circj.CJ-15-0448

    • NAID

      130005073137

    • ISSN
      1346-9843, 1347-4820
    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Olmesartan inhibits cultured rat aortic smooth muscle cell death induced by cyclic mechanical stretch through the inhibition of the c-Jun N-terminal kinase and p38 signaling pathways2015

    • Author(s)
      Satoyasu Ito, Kentaro Ozawa, Jing Zhao, Yoji Kyotani, Kosuke Nagayama, Masanori Yoshizumi
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 127 Issue: 1 Pages: 69-74

    • DOI

      10.1016/j.jphs.2014.11.002

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Azelnidipine inhibits cultured rat vascular smooth muscle cell death induced by cyclic mechanical stretch2014

    • Author(s)
      Jing Zhao, Kentaro Ozawa, Yoji Kyotani, Kosuke Nagayama, Satoyasu Ito, Akira T Komatsubara, Yuichi Tsuji, Masanori Yoshizumi
    • Journal Title

      PloS One

      Volume: 9 Issue: 7 Pages: e102813-e102813

    • DOI

      10.1371/journal.pone.0102813

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] 伸展負荷によるラット血管平滑筋細胞死に対するケモカインの保護作用2017

    • Author(s)
      趙晶、小澤健太郎、京谷陽司、吉栖正典
    • Organizer
      第90回日本薬理学会年会
    • Place of Presentation
      長崎ブリックホール
    • Year and Date
      2017-03-15
    • Related Report
      2016 Annual Research Report
  • [Presentation] 伸展刺激に対する血管平滑筋細胞応答と動脈硬化2017

    • Author(s)
      吉栖正典、趙晶、小澤健太郎、京谷陽司
    • Organizer
      第90回日本薬理学会年会
    • Place of Presentation
      長崎ブリックホール
    • Year and Date
      2017-03-15
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Chemokine inhibition of mechanical stretch-induced vascular smooth muscle cell death2016

    • Author(s)
      趙晶、小澤健太郎、京谷陽司、長山功佑、吉栖正典
    • Organizer
      第89回日本薬理学会年会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2016-03-09
    • Related Report
      2015 Research-status Report
  • [Presentation] Underlining mechanisms for arteriosclerosis in intermittent hypoxia or biomechanical stretch2016

    • Author(s)
      京谷 陽司、高澤 伸、趙 晶、小澤 健太郎、吉栖 正典
    • Organizer
      第89回日本薬理学会年会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2016-03-09
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] GLP-1 analogueであるExendin-4はアンジオテンシンIIによる血管平滑筋細胞の増殖と遊走を抑制する2016

    • Author(s)
      吉栖正典、長山 功佑、京谷 陽司、趙 晶、伊藤 都裕、小澤 健太郎
    • Organizer
      第45回日本心脈管作動物質学会
    • Place of Presentation
      阿波観光ホテル
    • Year and Date
      2016-02-05
    • Related Report
      2015 Research-status Report
  • [Presentation] 遺伝子編集を用いた内因性parkinへの一酸化窒素修飾のミトコンドリア機能への役割の検討2016

    • Author(s)
      小澤 健太郎、趙 晶、吉栖 正典
    • Organizer
      第129回日本薬理学会近畿部会
    • Place of Presentation
      広島県医師会館
    • Related Report
      2016 Annual Research Report
  • [Presentation] ケモカインによるストレッチ誘導性血管平滑筋細胞死の抑制2016

    • Author(s)
      小澤健太郎、趙晶、吉栖正典
    • Organizer
      第23回大阪市大フォーラム
    • Place of Presentation
      あべのメディックス
    • Related Report
      2016 Annual Research Report
  • [Presentation] 伸展負荷による血管平滑筋細胞死に対するケモカインの抑制作用2015

    • Author(s)
      趙晶、小澤健太郎、京谷陽司、長山功佑、吉栖正典
    • Organizer
      第25回 日本循環薬理学会
    • Place of Presentation
      東大寺総合文化センター
    • Year and Date
      2015-12-04
    • Related Report
      2015 Research-status Report
  • [Presentation] 蛍光タンパク質をもとにした高感度一酸化窒素評価法の開発2015

    • Author(s)
      小澤健太郎、辻 優一、小松原 晃、趙晶、吉栖正典
    • Organizer
      第25回 日本循環薬理学会
    • Place of Presentation
      東大寺総合文化センター
    • Year and Date
      2015-12-04
    • Related Report
      2015 Research-status Report
  • [Presentation] アンギオテンシンIIによる血管平滑筋細胞の増殖と遊走に対するGLP-1 analogueのExendin-4の抑制効果2015

    • Author(s)
      長山 功佑、京谷 陽司、趙 晶、伊藤 都裕、小澤 健太郎、吉栖 正典
    • Organizer
      第25回 日本循環薬理学会
    • Place of Presentation
      東大寺総合文化センター
    • Year and Date
      2015-12-04
    • Related Report
      2015 Research-status Report
  • [Presentation] オルメサルタンは、JNK及びp38シグナル経路を抑制する事で、周期的機械的伸展による培養大動脈平滑筋細胞死を抑制する2015

    • Author(s)
      伊藤都裕、小澤健太郎、趙晶、京谷陽司、長山功佑、吉栖正典
    • Organizer
      第88回日本薬理学会年会
    • Place of Presentation
      名古屋国際会議場
    • Year and Date
      2015-03-18 – 2015-03-20
    • Related Report
      2014 Research-status Report
  • [Presentation] 蛍光タンパク質を使った一酸化窒素アッセイ系の確立2015

    • Author(s)
      小澤 健太郎、辻 優一、趙 晶、伊藤 都裕、長山 功佑、京谷 陽司、吉栖 正典
    • Organizer
      第88回日本薬理学会年会
    • Place of Presentation
      名古屋国際会議場
    • Year and Date
      2015-03-18 – 2015-03-20
    • Related Report
      2014 Research-status Report
  • [Presentation] Sleep apnea Syndrome as an emerging risk factor for type 2 diabetes and atherosclerosis: evidence and underlying mechanism2014

    • Author(s)
      Yoji Kyotani, Hiroko Ota, Asako Itaya-Hironaka, Akiyo Yamauchi, Sumiyo Sakuramoto-Tsuchida, Jing Zhao, Kosuke nagayama, Kentaro Ozawa, Shin Takasawa, Hiroshi Kimura, Masanori Yoshizumi
    • Organizer
      9th Metabolic Syndrome, Type 2 diabetes and Aterosclerosis Congress
    • Place of Presentation
      京都国際会議場
    • Year and Date
      2014-09-12 – 2014-09-14
    • Related Report
      2014 Research-status Report
  • [Presentation] 一酸化窒素による脱分極ミトコンドリアの分解の制御機構2014

    • Author(s)
      小澤 健太郎、趙 晶、京谷 陽司、伊藤 都裕、長山 功佑、辻 優一、吉栖 正典
    • Organizer
      第37回日本神経科学大会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2014-09-11 – 2014-09-13
    • Related Report
      2014 Research-status Report
  • [Presentation] オルメサルタンはJNK、p38のリン酸化を阻害することにより伸展刺激による細胞死を抑制する2014

    • Author(s)
      伊藤都裕、趙晶、京谷陽司、長山功佑、辻優一、小澤健太郎、吉栖正典
    • Organizer
      第125回日本薬理学会近畿部会
    • Place of Presentation
      岡山コンベンションセンター
    • Year and Date
      2014-06-20
    • Related Report
      2014 Research-status Report
  • [Remarks] http://www.naramed-u.ac.jp/~pha/

    • Related Report
      2016 Annual Research Report
  • [Remarks] http//www.naramed-u.ac.jp/~pha/

    • Related Report
      2015 Research-status Report
  • [Remarks] http//www.naramed-u.ac.jp/~pha/

    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2018-03-22  

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