ペロキシソーム増殖因子によって活性化された受容体は,転写ノードルポイントと治療標的として機能する
Jonathan D Brown1, Jorge Plutzky
1Cardiovascular Division, Brigham and Women's Hospital, Boston, Mass, USA.
Circulation
|January 31, 2007
まとめ
ペロキシソーム増殖器活性化受容体 (PPARs) は,代謝と炎症を調節する. PPARアゴニストは心血管疾患の治療に有望な効果を示しているが,臨床試験の結果は混在しており,PPARの生物学に関するさらなる研究が必要である.
科学分野:
- 分子生物学は分子生物学である.
- メタボリック研究
- 心血管科学 心血管科学
背景:
- ペロキシソーム増殖器活性化受容体 (PPARs) は,脂質代謝,アディポゲネシス,およびインスリン感受性を調節する核受容体です.
- PPARの3つの同型 (アルファ,ガンマ,デルタ) はすべて炎症および動脈硬化経路に関与しています.
- PPARは,複数の遺伝子標的を制御することによって,代謝および血管機能を統合します.
研究 の 目的:
- 代謝経路と血管経路におけるPPARの役割を検討する.
- 心血管疾患の治療標的としてPPARを評価する.
- 既存の臨床試験データを分析し,将来のPPAR調節器の開発を導く.
主な方法:
- in vitro,動物モデル,およびヒトの代理マーカーの研究のレビュー.
- PPARアゴニストの研究から得られた臨床試験データの分析.
- PPAR機能の基礎となる生物学的メカニズムの検討.
主要な成果:
- PPARは確立された薬物標的であり,線維酸 (PPAR-alpha) とチアゾリジンジオン (PPAR-gamma) が臨床で使用されています.
- 証拠は,PPARの活性化が炎症と動脈硬化症を減らす可能性があることを示唆しています.
- PPARアゴニストによる初期の大規模な心血管疾患試験は,異なった結果をもたらしました.
結論:
- PPARは,エネルギーバランスと血管の健康を統合する重要なノードを表しています.
- 臨床試験の結果が異なっていたにもかかわらず,PPARは依然として有望な治療目標である.
- PPARベースの治療法を進歩させるために,PPARの生物学をより深く理解することが不可欠です.
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