S100a8/a9 シグナル伝達 ミトコンドリア機能不全と心臓肌細胞死因
Yulin Li1, Boya Chen1, Xinying Yang1
1Beijing Anzhen Hospital of Capital Medical University and Beijing Institute of Heart Lung and Blood Vessel Diseases, China (Y. Li, B.C., Z.Y., C.Z., Y.J., P.L., Y. Liu, Z.L., B.Q., J.D.).
Circulation
|June 22, 2019
まとめ
心筋不全-再注射 (MI/R) 損傷は重大な状態です. この研究は,S100a8/a9を心筋梗塞/心筋回路損傷の重要な媒介体として特定し,心臓発作の回復のための潜在的な治療目標を提供している.
科学分野:
- 心血管研究
- 分子医学
- プロテオミクスとゲノミクス
背景:
- 心筋不全再注射 (MI/ R) 損傷は,治療の選択肢が限られている重大な臨床的課題です.
- 偏見のないオミックスのアプローチは,MI/Rの新たなメディエーターを特定するのに不可欠です.
研究 の 目的:
- ダイナミック・トランスクリプトーム分析を用いてMI/Rの早期メディエーターを特定する.
- MI/Rの損傷におけるS100a8/a9の役割とメカニズムを解明する.
- 急性心筋梗塞の患者におけるS100a8/ a9の臨床的関連性を調査する.
主な方法:
- MI/Rを受けたマウスの心臓のダイナミック・トランスクリプトーム分析
- S100a8/a9の機能喪失と機能獲得に関する研究
- 心臓発作後の血清S100a8/ a9値の測定と主要な心血管疾患の追跡.
主要な成果:
- S100a8/ a9は,早期再注射中に最も上調された遺伝子として特定されました.
- S100a9 ノックアウトは心臓機能を改善し,過剰発現は損傷を悪化させた.
- S100a8/ a9は,TLR4/ ERK/ PPARGC1A/ NRF1シグナル伝達による複合体Iを阻害することによってミトコンドリア機能障害を引き起こした.
- S100a9 中和抗体の治療はMI/Rの損傷を減少させた.
- 心臓発作後の血清S100a8/ a9値上昇は,心血管不良と相関していた.
結論:
- S100a8/ a9は,ミトコンドリア機能を抑制することによって,早期MI/ R損傷における心筋細胞死亡の重要な調節剤である.
- S100a8/a9媒介のシグナリングをターゲットにすることは,MI/Rの損傷に対する有望な新しい治療戦略です.
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