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硫化水素の内生産量が減少すると,動脈硬化が加速する
Sarathi Mani1, Hongzhu Li, Ashley Untereiner
1Department of Biology, Lakehead University, Thunder Bay, ON, Canada.
Circulation
|May 25, 2013
まとめ
減少した硫化水素 (H2S) 生産は,動脈硬化症を加速します. シスタチオニン γ-ライアゼ (CSE) 欠乏したマウスの食事誘発性動脈硬化に対するNaHSの補充は,治療目標としてCSE/H2S経路を強調しています.
科学分野:
- 心血管生物学 心血管生物学
- メタボリック疾患の研究
- 動脈硬化症の病原性 病原性
背景:
- シスタチオニン γ-ライアゼ (CSE) は,心臓血管系における固有の硫化水素 (H2S) の生成に不可欠です.
- ネズミのCSE欠乏症は,H2Sレベルが低下し,血圧が上昇し,血管のリラックスが低下します.
- 動脈硬化症における内生的なH2S代謝の変化の直接的な役割は不明である.
研究 の 目的:
- 動脈硬化症の発症における内生性H2S生成の減少の因果的な役割を調査する.
- 動脈硬化症におけるCSE/H2S経路を標的とした治療の可能性を評価する.
主な方法:
- 6週間のCSE遺伝子ノックアウトと野生型のマウスは,12週間にわたってコントロールまたはアテロゲン的な食事を与えられました.
- 分析には,血脂質プロファイル,ホモシステイン,血圧,酸化ストレス,病変サイズ,細胞増殖,粘着分子発現が含まれていました.
- CSEノックアウトのマウスはNaHS,N-アセチルシステイン,またはエゼチミブで治療され,ダブルノックアウト (CSEとアポリポプロテインE) も研究されました.
主要な成果:
- アテロゲン性ダイエット中のCSEノックアウトマウスは,早期の脂肪線病変,高コレステロールおよびLDL,高ホモキステン血症,酸化ストレス増加,大動脈内膜増殖の増大を示した.
- NaHS治療はCSEノックアウトマウスの食事誘発性動脈硬化症を改善したが,N-アセチルシステインとエゼチミブは改善しなかった.
- CSEとアポリポプロテインE遺伝子の結合ノックアウトは,単一のノックアウトと比較して,動脈硬化症を悪化させた.
結論:
- CSE経路で合成される内生的なH2Sは,親密の増殖と粘着分子発現を減らすことによって,アテロゲン性損傷から保護します.
- 減少した内生的なH2S生産は,血管の再構築を促進し,動脈硬化症の発達を加速します.
- CSE/H2S経路は,動脈硬化症を予防するための重要な治療目標です.
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