Mechanisms of epicardial adipose tissue to cause atrial myocardial fibrosis and screening of compounds to suppress them
Project/Area Number |
19H04490
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Review Section |
Basic Section 90130:Medical systems-related
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Research Institution | Oita University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
安部 一太郎 大分大学, 医学部, 客員研究員 (00747595)
手嶋 泰之 大分大学, 医学部, 講師 (10457608)
宮本 伸二 大分大学, 医学部, 教授 (70253797)
福井 暁 大分大学, 医学部, 助教 (70631381)
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Project Period (FY) |
2019-04-01 – 2022-03-31
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Project Status |
Completed (Fiscal Year 2021)
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Budget Amount *help |
¥16,640,000 (Direct Cost: ¥12,800,000、Indirect Cost: ¥3,840,000)
Fiscal Year 2021: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2020: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2019: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
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Keywords | 心外膜脂肪 / 心房線維化 / 心房細動 / 線維化 / 炎症 |
Outline of Research at the Start |
心外膜脂肪の蓄積は心血管病発症を促進する。申請者らは心房細動患者の左心房標本を解析し,“心外膜脂肪と心房筋が接する箇所に線維化が生じ,心外膜脂肪中の悪玉サイトカインの量が線維化と相関すること”を解明した。しかし左心房標本は手術時の1点でしか得られないため“心外膜脂肪がどのような機序で心房線維化を惹起するかが不明”という課題が残った。本研究の目的は,“器官培養系を用いてヒト心外膜脂脂肪が心房線維化を惹起する機序を明らかにする”ことである。さらに病理解剖の御遺体を用い脂肪の部位による線維化様式の違いを解明する。そして“器官培養系を応用し心房線維化を抑制する化合物のスクリーニング系を構築する”。
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Outline of Final Research Achievements |
Objective: This study aimed to examine whether Angptl2 contained in peri-left atrial EAT can induce atrial myocardial fibrosis. Methods: Human peri-left atrial EAT and abdominal subcutaneous adipose tissue (SAT) were collected from 9 autopsy cases. EAT- or SAT-conditioned medium was dropped onto the rat left atrial epicardial surface using an organo-culture system. Results: EAT-conditioned medium induced atrial fibrosis with a progressive increase in the number of myofibroblasts. The profibrotic effect of EAT was greater than that of SAT. EAT in patients with atrial fibrillation induced a more significant atrial fibrosis. Treatment with human recombinant Angptl2 induced fibrosis, which was suppressed by the concomitant treatment with Angptl2 antibody. Conclusion: The results suggested that antagonizing the expression of Angptl2 in EAT can be a novel therapeutic approach to prevent atrial fibrillation.
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Academic Significance and Societal Importance of the Research Achievements |
心房細動は心房線維化によってもたらされる。本研究では,器官培養法という独創的な方法によって,ヒト心外膜脂肪が心房に線維化を惹起する様子を再現できた。また,Angptl2がこの経路に関与し,これを標的とした薬物を開発すれば,あらたな心房細動治療薬になり得ることを示すことができた。心房細動患者は本邦に数百万人いるとみられ少なからずの患者に脳梗塞を引き起こす。本研究の成果を心房細動阻止に結び付けたい。
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Report
(4 results)
Research Products
(12 results)
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[Journal Article] Role of angiopoietin-like protein 2 in atrial fibrosis induced by human epicardial adipose tissue: Analysis using an organo-culture system2020
Author(s)
Kira S, Abe I, Ishii Y, Miyoshi M, Oniki T, Arakane M, Daa T, Teshima Y, Yufu K, Shimada T, Takahashi N.
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Journal Title
Heart Rhythm
Volume: 17
Issue: 9
Pages: 1591-1601
DOI
Related Report
Peer Reviewed
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[Presentation] Detecting Fibrotic Remodeling of Epicardial Adipose Tissue in Patients with Atrial Fibrillation2021
Author(s)
Ishii Y, Abe I, harada T, Takano M, Kira S, Kondo H, Teshima Y, yufu K, Nakagawa M, Shimada T, Miyamoto S, Takahashi N.
Organizer
第85回日本循環器学会学術集会 3.26-28,2021. 横浜web
Related Report
Int'l Joint Research
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[Presentation] Possible Role of Endocardium of Left Atrial Appendage in Preventing the Thrombus2021
Author(s)
Ishii Y, Abe I, harada T, Takano M, Kondo H, Shinohara T, Teshima Y, yufu K, Nakagawa M, Shimada T, Miyamoto S, Takahashi N
Organizer
第85回日本循環器学会学術集会 3.26-28,2021. 横浜web
Related Report
Int'l Joint Research
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[Presentation] Loss of Rho effector mDia1 attenuates pressure overload-induced hypertrophic responses and exacerbates dysfunction.2020
Author(s)
Abe I, Ishii Y, Miyoshi M, Kira S, Kondo H, Saito S, Teshima Y, Yufu K, Terabayashi T, Ishizaki T, Takahashi N.
Organizer
第84回日本循環器学会学術集会
Related Report
Int'l Joint Research
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[Presentation] Role of the intramural adipose tissue of the interatrial septum on incidence of atrial fibrillation.2020
Author(s)
Abe I, Miyoshi M, Ishii Y, Kira S, Oniki T, Fukuda T, Fukui A, Shinohara T, Teshima Y, Nakagawa M, Takahashi N.
Organizer
第84回日本循環器学会学術集会
Related Report
Int'l Joint Research
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[Presentation] Role of angiopoietin-like protein 2 in atrial fibrosis induced by human epicardial adipose tissue.2020
Author(s)
吉良晋太朗 安部 一太郎, 石井 悠海, 三好 美帆, 鬼木 崇裕, 福井 暁, 篠原 徹二, 手嶋 泰之, 油布 邦夫, 島田 達夫, 中川 幹子, 高橋 尚彦
Organizer
第84回日本循環器学会学術集会
Related Report
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[Presentation] Human epicardial adipose tissue induces rat atrial myocardial fibrosis through paracrine effects: Results of organo-culture experiments2019
Author(s)
Shintaro Kira, Ichitaro Abe, Yumi Ishii, Miho Miyoshi, Takahiro Oniki, Akira Fukui, Tetsuji Shinohara, Yasushi Teshima, Kunio Yufu, Tatsuo Shimada, Mikiko Nakagawa, Naohiko Takahashi
Organizer
第83回日本循環器学会学術集会 3.29-31, 2019 横浜
Related Report
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