コレステリルエステル移転タンパク質の阻害による高密度リポプロテインコレステロールの増加 脂質不全症におけるコレステリルエステル移転タンパク質の増加:臨床医のための更新
James S Forrester1, Rajenda Makkar, P K Shah
1Cardiology Division, Cedars-Sinai Medical Center, Los Angeles, Calif 90048, USA. forrester@cshs.org
Circulation
|April 13, 2005
まとめ
低HDLコレステロールは重要なリスク因子です. コレステリルエステル転移タンパク質 (CETP) を阻害すると,HDLが効果的に上昇し,抗動脈硬化作用の潜在的な利点があります.
科学分野:
- 心血管医学は,心臓血管医学である.
- バイオケミストリー バイオケミストリー
- 薬理学 薬理学とは
背景:
- 高密度脂質タンパク質 (HDL) コレステロールの減少は,高密度脂質タンパク質 (LDL) コレステロールの上昇に匹敵する重要な心血管リスク因子です.
- HDLの介入は,潜在的に強化された逆コレステロール輸送と抗酸化/抗炎症作用を通じて,抗動脈硬化特性を示しています.
研究 の 目的:
- コレステリルエステル転送タンパク質 (CETP) 阻害がHDLレベルと動脈硬化に与える影響を調査する.
- ヒトにおけるCETP阻害薬の有効性を評価する.
主な方法:
- 高コレステロール血症のウサギの研究では,CETPの阻害により,HDLが50%以上増加することが示されました.
- CETPに影響するヒトの遺伝子変異とその動脈硬化リスクとの関連を調べる.
- ヒトに薬学的CETP阻害剤を投与し,HDLレベルの変化を評価する.
主要な成果:
- CETP阻害は,高脂血症では抗動脈硬化作用であるが,重度の高トリグリセリデミアでは効果が低い.
- 人間のCETP変異は,動脈硬化症との相反的な関連性を示し,文脈に依存する効果を示唆しています.
- 薬理学的CETP阻害剤は,ヒトのHDLを50%~100%増加させることができます.
結論:
- CETP阻害は,HDLを上昇させるための重要な進展であり,LDLに対するスタチンの効果に匹敵します.
- CETP阻害から最も恩恵を受ける特定の患者集団を特定するために,さらなる臨床試験が必要である.
- CETP阻害の抗動脈硬化作用は,患者の代謝プロファイルとCETP阻害の程度に依存する可能性があります.
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