Development of novel therapeutic strategy for persistent atrial fibrillation

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K09486
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: University of Tsukuba
• Principal Investigator: Murakoshi Nobuyuki 筑波大学, 医学医療系, 准教授 (80447218)
• Co-Investigator(Kenkyū-buntansha): 許 東洙 筑波大学, 医学医療系, 准教授 (20616651)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 不整脈 / 心房細動 / 異常電位 / 連続性分裂電位 / 培養細胞

Outline of Final Research Achievements

Cardiac myocyte cell line HL-1 cells were cocultured with cardiac fibroblasts, and treated with rapid electrical stimulation or treated with isoprotelenol (ISO). After treatment, electrophysiological properties were recorded by using multielectrode array system. ISO-treated cells showed the shortening of action potential duration (APD), and partially exhibited delayed afterdepolarization (DAD)-like potentials. Such cell clusters showed intracellular calcium overload, and alterations in expressions of calcium handling-related molecules. Screening for compound library, a natural compound was found to reduce the shortening of APD / the abnormal electrical activity. Angiotensin II (100 ng/kg/min)-administered wild-type mice showed atrial fibrosis progression, and atrial fibrillation (AF) prolongation, whereas treatment with the compound could partially inhibit the pathological phenotypes.

Free Research Field

循環器内科

Academic Significance and Societal Importance of the Research Achievements

心房細動は高齢者に多く、日本で100万人以上の患者がいると推定される不整脈疾患の一つであり、生活の質の低下、心不全・脳梗塞の発症リスクの上昇をもたらす。心房細動に対する薬物治療やカテーテルアブレーション治療が確立しているものの、高齢化社会の進展とともに患者数が増加しており、また持続性心房細動では再発率がなお高いのが問題である。本研究では病態の解明、新たな治療法・予防法の開発のために、病気を反映した培養細胞系を確立したこと、その培養系を用いたスクリーニングにより、心房細動を抑制しうる化合物を見出すことができたことが学術的意義である。本研究をさらに発展させ、心房細動の治療・予防の開発につなげたい。