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Pathophysiological mechanism for Ca2+ transport regulation in vascular remodeling and its therapeutic application

Research Project

Project/Area Number 19K07132
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 47040:Pharmacology-related
Research InstitutionTokushima Bunri University

Principal Investigator

Kita Satomi  徳島文理大学, 薬学部, 教授 (10461500)

Co-Investigator(Kenkyū-buntansha) 太田 紘也  徳島文理大学, 薬学部, 助教 (40638988)
喜多 知  福岡大学, 医学部, 講師 (50797107)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
KeywordsCa輸送制御 / 血管再構築 / Na/Ca輸送体
Outline of Research at the Start

肺動脈性肺高血圧症、末梢循環障害などの血管病は、血管内皮細胞・血管平滑筋細胞の機能異常(血管過収縮、血管リモデリング)により発症する。近年、血管病の病態形成機序や治療標的として、「病的・治療的血管再構築」が注目されている。本研究では、Na/Ca交換輸送体の血管内皮細胞・血管平滑筋細胞の機能異常(血管過収縮、血管リモデリング)への関与について、血管内皮・血管平滑筋特異的NCLX/NCX遺伝子改変マウスを駆使して、病的・治療的血管再構築に関わるCa輸送体を特定し、それを標的とした新規血管病治療戦略の提案を目指す。

Outline of Final Research Achievements

Vascular dysfunction and remodeling based on endothelial cell injury and vascular smooth muscle cell proliferation/hypercontraction are deeply involved in the onset of vascular diseases such as pulmonary arterial hypertension (PAH) and peripheral arterial disease. Such vascular diseases may be associated with endothelial and arterial Ca2+ handling abnormality, but the detailed molecular mechanisms are still unknown. In this study, we examined the possibility that Na/Ca exchangers participate in endothelial and arterial Ca2+ handling abnormality. Our results suggest that Ca2+ efflux via NCLX contributes to vascular dysfunction and remodeling.

Academic Significance and Societal Importance of the Research Achievements

ミトコンドリアはATPを産生する重要なオルガネラであるとともに、アポトーシスの誘導、活性酸素種(ROS)の生成など、細胞の生死に関わる多彩な機能を担っている。本研究により、ミトコンドリアから細胞質へのCa2+放出が血管新生、血管リモデリングおよび平滑筋収縮に機能的に働くことが示された。本研究により、NCLXの機能異常が血管病の発症に関与する可能性が示されたことから、NCLXが血管病の新たな治療標的として期待される。

Report

(4 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • Research Products

    (7 results)

All 2021 2020 2019

All Journal Article (2 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results,  Open Access: 1 results) Presentation (5 results)

  • [Journal Article] Genetic knockout and pharmacologic inhibition of NCX1 attenuate hypoxia-induced pulmonary arterial hypertension.2020

    • Author(s)
      1.Nagata A, Tagashira H, Kita S, Kita T, Nakajima N, Abe K, Iwasaki A, Iwamoto T.
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Volume: 529(3) Issue: 3 Pages: 793-798

    • DOI

      10.1016/j.bbrc.2020.06.045

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Aberrant Amygdala-Dependent Cued Fear Memory in Na+/Ca2+ Exchanger 1 Heterozygous Mice.2019

    • Author(s)
      Moriguchi S, Kita S, Inagaki R, Yabuki Y, Sasaki Y, Ishikawa S, Sakagami H, Iwamoto T, Fukunaga K.
    • Journal Title

      Mol Neurobiol

      Volume: 56 Issue: 6 Pages: 4381-4394

    • DOI

      10.1007/s12035-018-1384-2

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Presentation] Therapeutic strategy targeting NCX1 for pulmonary arterial hypertension2021

    • Author(s)
      Satomi Kita, Hideaki Tagashira, Takahiro Iwamoto
    • Organizer
      第95回日本薬理学会年会シンポジウム
    • Related Report
      2021 Annual Research Report
  • [Presentation] Involvement of mitochondrial Na+/Ca2+ exchanger in hypoxia-induced pulmonary arterial hypertension.2020

    • Author(s)
      1)Satomi Kita, Hideaki Tagashira, Tomo Kita, Ai Shinayama, Takahiro Iwamoto
    • Organizer
      第93回日本薬理学会年会
    • Related Report
      2020 Research-status Report
  • [Presentation] ミトコンドリアNa+/Ca2+交換輸送体は低酸素誘発性肺高血圧の発症に関与する.2020

    • Author(s)
      喜多紗斗美,田頭秀章,喜多知,品山愛,岩本隆宏
    • Organizer
      日本薬学会第140年会
    • Related Report
      2020 Research-status Report
  • [Presentation] 13)喜多紗斗美,田頭秀章,喜多知,品山愛,岩本隆宏,低酸素誘発肺高血圧症におけるミトコンドリアNa+/Ca2+交換輸送体の関与.2019

    • Author(s)
      喜多紗斗美,田頭秀章,喜多知,品山愛,岩本隆宏
    • Organizer
      第136回日本薬理学会近畿部会
    • Related Report
      2019 Research-status Report
  • [Presentation] 血管平滑筋NCX1機能異常による低酸素誘発肺高血圧発症機序2019

    • Author(s)
      田頭秀章,永田旭,喜多紗斗美,喜多知,阿部弘太郎,岩崎昭憲,岩本隆宏
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2023-01-30  

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