Mechanisms of epicardial adipose tissue to cause atrial myocardial fibrosis and screening of compounds to suppress them

2021 Fiscal Year Final Research Report

• Project/Area Number: 19H04490
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 90130:Medical systems-related
• Research Institution: Oita University
• Principal Investigator: Takahashi Naohiko 大分大学, 医学部, 教授 (30263239)
• 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)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 心外膜脂肪 / 心房線維化 / 心房細動

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.

Free Research Field

循環器内科

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。