心外膜脂肪の線維化を検出し心房細動ハイリスク患者を同定するCT画像診断法
| Project/Area Number |
21K19658
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 58:Society medicine, nursing, and related fields
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| Research Institution | Oita University |
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Principal Investigator |
高橋 尚彦 大分大学, 医学部, 教授 (30263239)
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| Project Period (FY) |
2021-07-09 – 2024-03-31
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| Project Status |
Granted (Fiscal Year 2022)
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| Budget Amount *help |
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2023: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2022: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2021: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 心外膜脂肪 / 心房細動 / CT値減衰度 |
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| Outline of Research at the Start |
心房細動患者は数百万人にのぼり脳梗塞を高率に発症する。申請者は心房細動に関する基礎研究を15年以上にわたって行ってきた。最近では心臓手術時に得られた59例の心房細動患者の左心耳切片を検討し“心外膜脂肪そのものの線維化が顕著であるほど，隣接する心房筋に炎症性心房線維化が強く生じる”という新事実を明らかにし，これを“Fibrotic EAT”と名付けた。このFibrotic EATには悪玉サイトカイン（IL-6，MCP-1，TNF-α）が多く含まれ心房細動を進行させることも突き止めた。本研究の目的は，このFibrotic EATを検出可能な新たなCT画像診断テクノロジーを開発することである。
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| Outline of Annual Research Achievements |
We previously investigated the role of EAT in AF in humans. Left atrial (LA) appendage samples were obtained from AF patients during cardiovascular surgery. Histologically, the severity of fibrotic EAT remodeling was associated with LA myocardial fibrosis. Total collagen in the LA myocardium (i.e., LA myocardial fibrosis) was positively correlated with proinflammatory and profibrotic cytokines/chemokines, including interleukin-6, monocyte chemoattractant protein-1, and tumor necrosis factor-α, in EAT. Human peri-LA EAT and abdominal subcutaneous adipose tissue (SAT) were obtained by autopsy. EAT- or SAT-derived conditioned medium was applied to the rat LA epicardial surface using an organo-culture system. EAT-conditioned medium induced atrial fibrosis in organo-cultured rat atrium. The profibrotic effect of EAT was greater than that of SAT. The fibrotic area of the organo-cultured rat atrium treated with EAT from patients with AF was greater than in patients without AF. Treatment with human recombinant angiopoietin-like protein 2 (Angptl2) induced fibrosis in organo-cultured rat atrium, which was suppressed by concomitant treatment with anti-Angptl2 antibody. Finally, we attempted to detect fibrotic EAT remodeling on computed tomography (CT) images, which demonstrated that the percent change in EAT fat attenuation was positively correlated with EAT fibrosis. Based on these findings, we conclude that the percent change in EAT fat attenuation determined using CT non-invasively detects EAT remodeling.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
「研究実績の概要」に記載したように，おおむね順調に進展している。
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| Strategy for Future Research Activity |
令和5年度は，大動脈弁狭窄症患者に拡げて解析予定である。
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Report
(2 results)
Research Products
(4 results)
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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
