心臓カルシトニンによるパラクリン信号は,心房線維生および心律乱を制御する
Lucia M Moreira1, Abhijit Takawale2,3, Mohit Hulsurkar4,5
1Division of Cardiovascular Medicine, Radcliffe Department of Medicine, British Heart Foundation Centre of Research Excellence, University of Oxford, John Radcliffe Hospital, Oxford, UK.
Nature
|November 5, 2020
まとめ
甲状腺ホルモンのカルシトニンは 心臓細胞によって生成され 線維症を制御します 低カルシトニンレベルは,心房細動患者におけるこの一般的な心律失調症の治療目標である可能性を示唆する.
科学分野:
- 心臓病科
- 内分泌学
- 分子生物学
背景:
- 心房細動 (AF) は,脳卒中と死亡率に関連した一般的な心律乱です.
- 心房線維症は AFの重要な特徴ですが その分子原因は不明です
- 現在のAF治療は不十分で 新しいメカニズムを研究する必要がある
研究 の 目的:
- 心房線維症と心房線維症におけるカルシトニンの役割を調査する.
- カルシトニンのパラクリンシグナル伝達を atrial cardiomyocytesとfibroblastsで調査する
- ヒトAF患者におけるカルシトニン濃度と受容体の発現を評価する.
主な方法:
- 胸前心筋細胞によるカルシトニン産生を調査した.
- カルシトニンとその受容体の遺伝子操作によるマウスモデルを使用した.
- ヒトAF患者における心筋カルシトニン濃度と線維細胞カルシトニン受容体の発現を分析した.
- 人間の心房線維細胞のトランスクリプトームとプロテオミック分析を行った.
主要な成果:
- カルシトニンは,繊維細胞の増殖と細胞外マトリックス分泌を制御するパラクリン信号として作用する.
- マウスにおける全局的なカルシトニン受容体の障害は,心房線維症と心房線維症の感受性を高めました.
- アトリアル特異カルシトニンのノックダウンにより,線維症とAFが悪化し,過剰発現が予防された.
- ヒトのAF患者では,心筋カルシトニンと線維細胞カルシトニン受容体のレベルが著しく低下した.
結論:
- 心筋カルシトニンのシグナル伝達は,心房線維症と心房動脈症の予防に不可欠です.
- カルシトニン信号の回復は AFの潜在的な治療戦略です
- カルシトニンの役割は骨の代謝を超えて心臓の健康に及ぶ.
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