不律性心筋病における免疫応答の治療的調節
Stephen P Chelko1, Angeliki Asimaki2, Justin Lowenthal3
1Departments of Medicine (S.P.C., D.B., N.A.-A., P.A.), Johns Hopkins School of Medicine, Baltimore, MD.
Circulation
|September 20, 2019
まとめ
炎症は不律性心筋病 (ACM) に重要な役割を果たします. 核因子-κBのシグナリングを阻害すると,ACMの特徴が低下し,この状態に対する新しい治療法を提供することができる.
科学分野:
- 心血管研究
- 分子生物学
- 免疫学
背景:
- 炎症は不律性心筋病 (ACM) の既知の特徴である.
- 炎症がACM疾患のフェノタイプに与える特定の寄与は不明である.
研究 の 目的:
- 核因子-κB (NF-κB) 信号がACMの病原性における役割を調査する.
- ACMにおけるNF-κBシグナリングの標的化による治療の可能性を評価する.
主な方法:
- in vitroおよびin vivo ACMモデルにおけるNF- kBシグナル活性化の特徴
- 患者の誘発性多能幹細胞 (iPSC) の心臓筋細胞を使用した.
- 特定のNF- kB阻害剤であるBay 11- 7082を投与し,ACMの特徴に対する効果を評価した.
主要な成果:
- NF- kBシグナリングは,インビトロおよびインビボACMモデル,および患者由来心筋細胞の両方で活性化されました.
- Bay 11- 7082によるNF- kBシグナル伝達抑制は,ミオサイトアポトーシス,サイトカインの放出,心臓機能障害,線維症を含む主要なACM特性を改善しました.
- 炎症性サイトカインとケモカインの濃度が低下したのは,治療を受けたマウスの心臓と患者の細胞で観察された.
結論:
- 活性化された炎症信号は,特にNF-κB経由で,ACMの病原性には不可欠です.
- 炎症経路を標的にすることは,ACMの有望な,メカニズムに基づく治療戦略です.
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