PPARalphaアゴニストは,ヒトモノサイトおよびマクロファージにおける組織因子の発現を阻害する
B P Neve1, D Corseaux, G Chinetti
1Département d'Athérosclérose, U.325 INSERM, Institut Pasteur de Lille, and the Faculté de Pharmacie, Université de Lille II, France.
Circulation
|February 24, 2001
まとめ
ペロキシソーム増殖器活性化受容体アルファ (PPARα) アゴニストは,繊維酸と同様に,単細胞とマクロファージにおける組織因子 (TF) 遺伝子発現を減少させます. これは,PPARαの活性化が,動脈硬化性プラークの血栓形成性を制御する可能性があることを示唆しています.
科学分野:
- 心血管生物学 心血管生物学
- 分子医学は分子医学である.
- トロンボシス研究研究
背景:
- モノサイト組織因子 (TF) 発現は,血管損傷における血栓性に影響を及ぼします.
- エンドトキシンは,ペロキシソーム増殖剤活性化受容体アルファ (PPARα) によって調節される経路であるAP-1とNF-kappaB経由でTF発現を誘導する.
研究 の 目的:
- 単細胞におけるTF発現に対する繊維酸および他のPPARαアゴニストの影響を調査する.
主な方法:
- THP-1細胞とヒト原生モノサイト/マクロファージにおけるPPARα発現を評価した.
- 測定されたTF mRNAと,PPARαアゴニスト (フェノ繊酸,WY14643,GW2331) の存在において,リポポリサッカリドまたはインタールヒキン-1βで刺激した後の活性.
主要な成果:
- PPARαタンパク質はTHP-1細胞で発現し,ヒトの原始単細胞と似ています.
- PPARαアゴニストは,細胞系と原細胞の両方で,リポポリサッカリドまたはインタールイキン-1βによって誘発されたTF mRNAのアップレギュレーションとTF活性を著しく抑制しました.
結論:
- PPARαの活性化は,TF遺伝子のダウンレギュレーションにつながります.
- PPARαは,モノサイトとマクロファージのTF発現を調節することによって,動脈硬化性プラークの血栓形成性を制御する新しい役割を果たします.
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