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2018 Fiscal Year Final Research Report

Epigenetic modification in hypertrophied nuclei of the cardiomyocytes and its pathophysiological significance

Research Project

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Project/Area Number 16K09509
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Cardiovascular medicine
Research InstitutionAsahi University

Principal Investigator

Genzou Takemura  朝日大学, 歯学部, 教授 (40283311)

Co-Investigator(Kenkyū-buntansha) 金森 寛充  岐阜大学, 医学部附属病院, 講師 (20456502)
岡田 英志  岐阜大学, 医学部附属病院, 講師 (30402176)
Research Collaborator MATSUO Hitoshi  
MIYAZAKI Nagisa  
Project Period (FY) 2016-04-01 – 2019-03-31
Keywordsエピジェネティクス / クロマチン・リモデリング / DNAメチル化 / 心不全 / 拡張型心筋症
Outline of Final Research Achievements

Methylated DNA was immunohistochemically detected in human endomyocardial biopsies. DNA methylation was greater in failing heart due to dilated cardiomyopathy (DCM, n=75) than in nonfailing hearts (n=20), of which increase was noted only in cardiomyocytes but not in other cell types. Methylated DNA predominantly localized on nuclear heterochromatin. DNA methylation was significantly correlated with hemodynamic parameters.
We treated 10-week-old delta-sarcoglycan deficient mice, an animal model of DCM, with 5-azacytidine, an inhibitor of DNA methylation at a dose of 1 mg/kg/day. Six weeks later, the survival rate was 100% in the treated mice while it was 69% in the vehicle-treated mice. We are now promoting the animal experiment by incorporating more mice and analyzing the cardiac tissue of the sacrificed mice pathologically and biochemically.

Free Research Field

循環器内科

Academic Significance and Societal Importance of the Research Achievements

心筋細胞の肥大した核は従来その機能的意味が不明であったが、エピジェネティク変化ならびに病態との関連を明らかにすることでその意味の重要性を明らかにすることができる。
心不全動物モデルを用いて、エピジェネティック介入(DNAメチル化阻害薬)により心筋症の病態に変化が見られれば現実的かつ新しい心不全治療法のヒントがえられる可能性がある。

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Published: 2020-03-30  

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