| Project/Area Number |
17K16018
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Cardiovascular medicine
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| Research Institution | Fukushima Medical University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 心不全 / エピジェネティクス / メチル化 / セルフリーDNA / メチル化解析 / エピジェネティックス |
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| Outline of Final Research Achievements |
The pressure-overload heart model by transverse aortic contraction in mice was generated. Analysis was performed by using the hypertrophic hearts at 1 week and failing hearts at 4 week after surgery. After bisulfite-conversion of the DNA was conducted, DNA methylation analysis by real-time PCR by methylation and unmethylated specific primers showed there were no differences between these diseased hearts and normal hearts in CpG island in ATP2A2 and Dux4.
Next, cell-free DNA (cfDNA) were isolated from the serum samples of the patients with heart failure. Quantitative analysis of cfDNA by real-time PCR using LINE1 primer, levels of cfDNA were significantly increased in heart failure patients compared to the subject without heart failure. In the methylation analysis of cfDNA, due to the small amount of cfDNA, digital PCR would be needed to conduct further analysis of cfDNA methylation.
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| Academic Significance and Societal Importance of the Research Achievements |
循環血中セルフリーDNAは主に悪性腫瘍において研究が行われているが、心臓、とくに心不全におけるその意義については明確ではない。本研究では、心不全患者では、心不全を有さない対象と比較して、セルフリーDNAの有意な増加を認めた。方法論としてさらなる検討が必要であるが、心不全の病態・重症度に応じた特異的なDNAメチル化を同定しその程度を評価し得れば、メチル化セルフリーDNAが新たなバイオマーカー・予後指標になる可能性があると考えられ、引き続き解析を進める予定である。
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