ペロキシソーム増殖器活性化受容体のガンマ活性化剤は,血管の滑らかな筋肉細胞のアンジオテンシンII型1受容体をダウン調節する
K Takeda1, T Ichiki, T Tokunou
1Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.
Circulation
|October 12, 2000
まとめ
ペロキシソーム増殖器活性化受容体ガンマ (PPARgamma) アクティベータは,血管の滑らかな筋肉細胞におけるアニオテンシンII型1受容体 (AT(1) -R) の発現を減少させます. このダウンレギュレーションは,PPARgammaアクティベーターがネオインティマルの形成を阻害する方法を説明するかもしれません.
科学分野:
- 血管生物学 血管生物学
- 薬理学 薬理学とは
- 分子医学は分子医学である.
背景:
- トログリタゾンのようなペロキシソーム増殖器活性化受容体ガンマ (PPARgamma) アクティベータは,インスリン抵抗性を改善し,ネオインティマルの形成を抑制します.
- PPARガンマ活性化剤がネオインティマルの形成を抑制する正確なメカニズムは完全に理解されていません.
- アンジオテンシンII (Ang II) は,動脈硬化症,高血圧,および血管新生手術後のネオインティマルの増殖に関与しています.
研究 の 目的:
- 血管の滑らかな筋肉細胞 (VSMC) のアニオテンシンII型1受容体 (AT(1) -R) 発現に対するPPARガンマ活性化剤の効果を調査する.
主な方法:
- ノーザンブロットおよび放射性リガンド結合測定を用いて,AT(1) -R mRNAおよびタンパク質レベルの定量化.
- Ang IIに対するVSMCカルシウム反応の評価.
- ルシフェラーゼアッセイでAT(1) -Rプロモーターの活性とmRNAの安定性を測定する.
主要な成果:
- 天然および合成のPPARガンマ活性化剤 (15-デオキシ-デルタ12,14) -プロスタグランディンJ2およびトログリタゾン) は,VSMCにおけるAT1) -RmRNAおよびタンパク質発現を著しく低下させた.
- PPARガンマ活性化剤は,Ang IIに対するVSMCのカルシウム反応を弱めた.
- AT(1) -Rの抑制は,プロモーターの活性が低下し,mRNAの安定性が影響を受けていないことが示すように,転写レベルで発生しました.
結論:
- PPARガンマ活性化剤は,VSMCにおけるAT(1) -R発現と,その後のAng IIに対するカルシウム反応を効果的に低下させる.
- PPARgamma活性化剤によるAT(1)-Rのダウンレギュレーションは,ネオインティマル形成の抑制に貢献する重要なメカニズムである可能性があります.
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