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Omics analysis for stabilization mechanizm of carotid plaques based on the classification with calcium score

Research Project

Project/Area Number 18K08977
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 56010:Neurosurgery-related
Research InstitutionNagoya City University

Principal Investigator

Katano Hiroyuki  名古屋市立大学, 医薬学総合研究院(医学), 准教授 (30295612)

Project Period (FY) 2018-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords頚動脈狭窄症 / 頸動脈プラーク / 石灰化 / ゲノム / エピゲノム / 頸動脈狭窄症 / 石灰化プラーク / 頚動脈プラーク / DNA methylation / carotid plaque / calcification / carotid endarterectomy / carotid stenosis / carotiid plaque / calcium score / while exome sequencing / calcified plaque / genome / epigenome
Outline of Final Research Achievements

In severely calcified carotid artery plaques, enhanced ANGPTL4 expression was presumably induced mainly in association with the suppression of angiogenesis, together with suppression of FGFR2 expression, and ANGPTL4 was found to be a possible target gene of hsa-miR-4530 and hsa-miR-133b by the TargetScan algorithm, suggesting that ANGPTL4 action was enhanced by suppression of these miRNAs at the miRNA level, and that angiogenesis was suppressed. In addition, the characteristics of genomic mutations were compared between the highly calcified and low calcified groups of carotid artery plaques by whole exome analysis, and differences in single nucleotide polymorphisms of genes involved in vascular calcification and embolism were found.

Academic Significance and Societal Importance of the Research Achievements

頚動脈高度石灰化粥腫においてANGPTL4作用が増強され、miRNAレベルでも本因子に関連して血管新生が抑制される方向で調整されていること、および血管石灰化に関与するDNA一塩基多型の差異を明らかにし、特にANGPTL4を中心としたゲノム、エピゲノム変異による修飾、調節が、頚動脈粥腫の症候化予防の手掛かりとなる可能性を示した。将来的に症候率の高い、一般的には石灰化の少ない不安定プラークと呼ばれる粥腫において、症候化を抑え安定化を図るために血管新生抑制遺伝子の導入あるいは、血管新生促進遺伝子をtargetとするmicroRNA導入などの遺伝子治療への応用が考えられる。

Report

(7 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (10 results)

All 2023 2022 2021 2020 2019

All Journal Article (2 results) (of which Peer Reviewed: 2 results) Presentation (8 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results)

  • [Journal Article] Long non-coding RNA expression in calcified carotid plaques2023

    • Author(s)
      Katano H.、Mase M.
    • Journal Title

      Atherosclerosis

      Volume: 379 Pages: S31-S32

    • DOI

      10.1016/j.atherosclerosis.2023.06.151

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Differential Methylation Signatures in Severely Calcified Carotid Plaques by Genome-Wide Comprehensive Analysis2020

    • Author(s)
      Katano H, Nishikawa Y, Yamada H, Yamanaka T, Mase M
    • Journal Title

      Curr Neurovasc Res

      Volume: 17 Issue: 5 Pages: 534-628

    • DOI

      10.2174/1567202617666201029145028

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Presentation] 頚動脈プラーク安定化機構解明のための遺伝子解析2023

    • Author(s)
      片野広之、西川祐介、内田 充、山中智康、間瀬光人
    • Organizer
      第48回日本脳卒中学会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 高カルシウムスコアの頚動脈プラークのエピゲノム変異2022

    • Author(s)
      片野広之、西川祐介、内田 充、山中智康、間瀬光人
    • Organizer
      第47回日本脳卒中学会
    • Related Report
      2022 Research-status Report
  • [Presentation] 頚動脈病変とlong non-coding RNA発現2022

    • Author(s)
      片野広之、西川祐介、内田 充、山中智康、間瀬光人
    • Organizer
      第81回日本脳神経外科学会総会
    • Related Report
      2022 Research-status Report
  • [Presentation] 頚動脈狭窄症における高度石灰化粥腫の網羅的ゲノム・エピゲノム解析2021

    • Author(s)
      片野広之、西川祐介、内田 充、山田和雄、間瀬光人
    • Organizer
      第80回日本脳神経外科学会総会
    • Related Report
      2021 Research-status Report
  • [Presentation] 頚動脈病変の遺伝子発現:石灰化粥腫の安定性を支えているもの2021

    • Author(s)
      片野広之、西川祐介、山田和雄、間瀬光人
    • Organizer
      第46回日本脳卒中学会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] Molecular stabilizing mechanism in calcified carotid plaques2020

    • Author(s)
      Katano H, Mase M
    • Organizer
      The 88th European Atherosclerosis Society Congress (EAS 2020)
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] 高度石灰化頚動脈プラークのゲノム変異2019

    • Author(s)
      片野広之、西川祐介、鳥飼武司、間瀬光人
    • Organizer
      第78回日本脳神経外科学会総会
    • Related Report
      2019 Research-status Report
  • [Presentation] 全エクソーム解析による頚動脈石灰化粥腫の一塩基多型の検出2019

    • Author(s)
      片野広之、西川祐介、柴田帝式、間瀬光人
    • Organizer
      第48回日本脳卒中の外科学会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2025-01-30  

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