BET抑制は,炎症に起因する心臓機能不全とSARS-CoV-2感染を阻害する
Richard J Mills1, Sean J Humphrey2, Patrick R J Fortuna1
1QIMR Berghofer Medical Research Institute, Brisbane 4006, QLD, Australia.
Cell
|April 3, 2021
まとめ
COVID-19は炎症によって心臓損傷を引き起こす. ブロモドメインとエクストラトミナルファミリー阻害剤 (BETi) は,心臓機能障害と死亡をモデルで予防し,潜在的な治療戦略を提供することを示しています.
科学分野:
- 心臓病科
- ウイルス学
- 分子生物学
背景:
- COVID-19は心臓損傷と死亡率に関連しています.
- メカニズムは直接的なウイルス感染や炎症誘発の心臓機能障害を含む.
- 治療目標の特定は,COVID-19の心臓への影響管理に不可欠です.
研究 の 目的:
- COVID-19による心臓機能不全のメカニズムを解明する.
- COVID-19に対する潜在的心臓保護薬の特定
主な方法:
- 人間の心臓器官 (hCOs) とK18-hACE2マウスモデルを使用した.
- フォスフォプロテオミクスと単核RNA配列を用いました.
- 炎症刺激とBET阻害剤の効果を研究した.
主要な成果:
- "サイトカイン・ストーム" (インターフェロン・ガンマ,インタールイキン1β,ポリ・I:C) によって誘発された静脈機能不全.
- ブロモドメインを含むタンパク質4の活性化とウイルス反応は,hCOとマウスモデルで観察された.
- BET阻害剤 (BETi) はhCOの心臓機能を回復し,マウスの死亡を予防した.
- BETiはウイルスの遺伝子転写,ACE2発現,および心筋細胞感染を減少させた.
結論:
- アパベトロンを含むBETiは,COVID-19によって引き起こされる心臓機能障害と死亡率に効果的に抵抗します.
- BETiは,COVID-19患者の心臓損傷を予防する有望な治療候補である.
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