2022 Fiscal Year Final Research Report

Secretome analysis of human epicardial adipose tissue in atrial fibrillaiton: exploiting novel pathophysiology and biomarkers

Research Project

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Project/Area Number	20K08501
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 53020:Cardiology-related
Research Institution	Fujita Health University
Principal Investigator	Harada Masahide 藤田医科大学, 医学部, 准教授 (70514800)
Co-Investigator(Kenkyū-buntansha)	井澤英夫藤田医科大学, 医学部, 教授 (80402569) 高木靖藤田医科大学, 医学部, 教授 (80324432) 尾崎行男藤田医科大学, 医学部, 教授 (50298569) 渡邉英一藤田医科大学, 医学部, 教授 (80343656)
Project Period (FY)	2020-04-01 – 2023-03-31
Keywords	心房細動 / 心外膜脂肪組織 / 心房リモデリング
Outline of Final Research Achievements	RNA sequencing, proteomic analysis, qPCR and western blotting were performed in left (LA) and right atrial (RA) tissues from atrial fibrillation (AF) patients; the regional differences of gene/protein expression profiles were comprehensively analyzed. In the results, bone morphogenic protein 10 (BMP10, a growth factor) expression increased in the RA whereas paired like homeodomain 2 (PITX2, a transcription factor) expression increased in the LA, suggesting that the regional differences may underlie the LA-RA difference in pathological profile/progression of atrial remodeling in AF. In ingenuity pathway analysis (IPA), BMP10-related signaling contributes to the regional differences of atrial remodeling and specific miRNA-dependent mechanisms were suggested. We investigate the effects of BMP10 on cellular function and PITX2 transcriptional activity in cultured cardiomyocyte/cardiac fibroblasts. We also evaluate the efficacy of the exosome-derived miRNA as clinical biomarkers in AF.
Free Research Field	循環器分野
Academic Significance and Societal Importance of the Research Achievements	AFにおける心房リモデリングの左右差の機序が解明されれば、左房に特異的な血栓形成の予防や心房リモデリングの抑制につながる可能性がある。また、分泌・液性調節臓器としての心房の役割が真実であるなら、未知の心房機能の発見であり、学術的な意義も極めて大きい。新たな臨床バイオマーカーによる治療効果、病態の進行、合併症の発症などが予測できるようになれば、個別化医療が実現でき、AFの治療成績や生命予後を劇的に改善させる可能性がある。AFは実臨床で最も頻度の高い不整脈であり、本研究によってAFの臨床マネージメントが革新的に進歩すれば、社会的、医療経済的な貢献度は計り知れない。