血酸化低密度リポプロテイン除去が動脈硬化に与える影響
Yasushi Ishigaki1, Hideki Katagiri, Junhong Gao
1Division of Molecular Metabolism and Diabetes, Tohoku University Graduate School of Medicine, Sendai, Japan.
Circulation
|June 19, 2008
まとめ
総LDLコレステロールだけでなく,酸化LDL (oxLDL) の除去をターゲットにすることで,動脈硬化症の進行を著しく抑制します. この研究では,肝臓のoxLDL受容体LOX-1を強化することで,マウスの動脈疾患を予防することが示されています.
科学分野:
- 心血管科学の研究について
- 動脈硬化症 (Atherosclerosis) とは 動脈硬化症 (Atherosclerosis) とは 動脈硬化症 (Atherosclerosis) とは
- 脂質代謝についてです.
背景:
- スタチンの治療はLDLコレステロールを低下させ,心血管疾患による死亡率を低下させます.
- 酸化LDL (oxLDL) は,動脈硬化症の発達に関与しています.
- 単にoxLDLを減らすだけでアテロゲネシスに与える特定の影響は,完全に理解されていません.
研究 の 目的:
- oxLDL.DLのアテロゲン作用を調査する.
- oxLDLをターゲットにすると,動脈硬化に直接影響があるかどうかを判断する.
- 動脈硬化症の予防における肝臓のレクチン状オックスLDL受容体1 (LOX-1) 発現の有効性を調査する.
主な方法:
- アデノウイルス媒介によるLOX-1の肝発現は,アポリポプロテインE欠乏症のマウスで.
- オイルレッドO染色による動脈硬化性病変の進行の評価.
- 血のオックスLDL,単細胞化学毒性タンパク質-1,脂質過酸化物,アディポネクチン濃度の測定.
主要な成果:
- 肝臓のLOX-1発現は,肝臓でのoxLDLの吸収を成功裏に増加させました.
- 血のoxLDL濃度は,LOX-1を発現するマウスにおいて,一時的に有意に低下した.
- 動脈硬化性病変の進行は,対照群と比較して,LOX-1マウスではほぼ完全に抑制されました.
- 系統的酸化ストレスマーカーは減少し,単細胞化学反応性タンパク質-1と脂質過酸化物の減少とアディポネクチンの増加によって示されています.
結論:
- 酸化されたLDLは,動脈硬化症を誘発する上で重要な役割を果たします.
- 特に肝臓のLOX-1経由でのoxLDL除去をターゲットにすることは,有望な治療戦略です.
- オックスLDLを減らすことは,継続的に高いLDLコレステロールがある場合でも,動脈硬化症の進行を防ぐことができます.
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