外部化ヒストンH4は,リティック細胞死を引き起こすことで慢性炎症を誘導する
Carlos Silvestre-Roig1,2,3, Quinte Braster4,5,6, Kanin Wichapong7
1Institute for Cardiovascular Prevention (IPEK), LMU München, Munich, Germany. carlos.silvestre@med.uni-muenchen.de.
Nature
|May 3, 2019
まとめ
細胞外ヒストンH4は,滑らかな筋肉の細胞死と動脈損傷を引き起こします. ヒストンH4を中和させることで細胞死が防ぎ,動脈硬化病変を安定させ,慢性血管疾患の治療対象となる可能性がある.
科学分野:
- 心血管生物学
- 免疫学
- 細胞 死 の 仕組み
背景:
- 慢性的な炎症は 世界的な健康問題です
- 非プログラム細胞死は慢性炎症に寄与しますが,その誘発と媒介者は不明です.
- 死因の1つである動脈硬化症は 動脈の炎症とプラークの不安定性を含みます
研究 の 目的:
- 滑らかな筋肉細胞死と動脈硬化における炎症における細胞外ヒストンH4の役割を調査する.
- 血管疾患における炎症の細胞および分子メディエーターを特定する.
- ヒストンH4を標的とした治療戦略を探求する.
主な方法:
- 動脈硬化症のマウスモデルを使用しました
- 細胞外ヒストンH4と滑らかな筋肉細胞 (SMC) の相互作用を調査した.
- 中性粒子の細胞外トラップ (NET) の形成とヒストンH4の放出を分析した.
- ヒストンH4中和がSMC死亡とプラークの安定性に与える影響を評価した.
主要な成果:
- 細胞外ヒストンH4はSMCの膜解離を介し,動脈組織損傷と炎症を引き起こす.
- 活性化されたSMCは中性粒子を誘導し,ヒストンH4のような核タンパク質を含むNETの放出につながる.
- ヒストンH4がSMCに結合すると,細胞死とプラークの不安定化が発生し,その中和によりSMCの死が防ぎ,病変が安定する.
結論:
- 慢性血管疾患における 白血球による細胞死という 新しい形態を特定しました
- 細胞外ヒストンH4は,SMC死亡と動脈硬化性プラークの不安定性の主要な媒介です.
- 細胞外ヒストンH4を標的とした治療は 動脈硬化症やそれに関連する慢性血管疾患の 治療方法として有望です
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