| Project/Area Number |
18K08977
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 56010:Neurosurgery-related
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| Research Institution | Nagoya City University |
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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)
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| Project Period (FY) |
2018-04-01 – 2024-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| 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)
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| 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 |
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| 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.
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| 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。
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