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Study of the Actin Cytoskeleton in Live Endothelial Cells Expressing GFP-Actin
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トロンビンは,RhoA/ROCK経路経由でヒト内皮アルギナゼの酵素活性を刺激する:動脈硬化内皮機能不全への影響
Xiu-Fen Ming1, Christine Barandier, Hema Viswambharan
1Vascular Biology, Department of Medicine, Division of Physiology, University of Fribourg, Fribourg, Switzerland.
Circulation
|December 1, 2004
まとめ
トロンビンは,内皮細胞のRhoA/ROCKを通じてアルギナース活性を増大させる. この増加した活動は,動脈硬化症の内皮機能不全に寄与し,アルギナゼを治療標的として示唆しています.
科学分野:
- 血管生物学 血管生物学
- バイオケミストリー バイオケミストリー
- 心血管研究 循環器科の研究
背景:
- アルギナゼは,L-アルギニンのための内皮酸化窒素合成酵素 (eNOS) と競合し,酸化窒素 (NO) の生成を減少させます.
- アルギナース調節の理解は,内皮機能不全と動脈硬化症の治療に不可欠です.
研究 の 目的:
- 内皮細胞におけるアルギナース活性に関する規制メカニズムを調査する.
- 動脈硬化症の病原性におけるアルギナースの役割を決定する.
主な方法:
- トロンビンによって刺激されたヒト静脈内皮細胞におけるアルギナゼの活性評価.
- RhoA/ROCK経路の阻害剤とアクティベーターを用いて信号伝達を研究した.
- 動脈硬化症のアポE-/-マウスにおけるアルギナーゼIIとRhoAのレベルを分析した.
- マウスモデルでL-アルギニンとアルギナース抑制に対する血管の反応を調べた.
主要な成果:
- トロンビン投与量および時間に依存した,RhoA/ROCK経路経由によるアルギナゼ活性の増加.
- アクティブなRhoAとROCK変異体は,アルギナース活性を大幅に高めました.
- アルギナーゼII活性とRhoA濃度の上昇は,動脈硬化症のマウス大動脈で観察されました.
- アルギナース抑制は,動脈硬化症のマウスの血管拡張を改善しました.
結論:
- トロンビンは,RhoA/ROCK経路を通じて,内皮アルギナゼの活性を刺激する.
- アルギナーゼの活性が増加すると,動脈硬化症における内皮機能不全に寄与する.
- 血管アルギナーゼをターゲットにすることは,動脈硬化症の潜在的な治療戦略です.
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