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LRP:血管壁の整合性と動脈硬化からの保護における役割
Philippe Boucher1, Michael Gotthardt, Wei-Ping Li
1Department of Molecular Genetics, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9046, USA.
Science (New York, N.Y.)
|April 12, 2003
まとめ
低密度リポプロテイン受容体関連タンパク質 (LRP1) は,PDGF受容体 (PDGFR) 信号伝達を調節することによって,血管の滑らかな筋肉細胞の移動と動脈硬化を防ぐ. LRP1を非活性化すると,PDGFRが過剰発現し,血管の損傷と疾患を促します.
科学分野:
- 心血管生物学 心血管生物学
- 動脈硬化症の研究 動脈硬化症の研究
- 分子医学は分子医学である.
背景:
- 血管の滑らかな筋肉細胞 (SMC) の増殖と移動は,動脈硬化症の発達における重要なプロセスです.
- 血小板由来成長因子 (PDGF) 信号伝達は,SMCの移動に影響を与え,低密度リポプロテイン受容体関連タンパク質 (LRP1) は通常,この効果を抑制する.
研究 の 目的:
- 血管性SMCにおけるPDGF受容体 (PDGFR) 信号伝達の調節におけるLRP1の役割を調査する.
- LRP1不活性化が血管の整体性や動脈硬化症の発達に及ぼす影響を判断する.
主な方法:
- 血管性SMCにおけるLRP1とPDGFRの相互作用を調査した.
- 血管SMCで不活性化されたLRP1を持つ遺伝子組み換えマウスを利用した.
- 血管異常,SMC増殖,動脈硬化感受性を評価した.
- Gleevec (PDGFシグナル伝達阻害剤) の疾患発症に対する効果を評価した.
主要な成果:
- LRP1はPDGFR.と複合体を形成する.
- マウスにおけるLRP1の不活性化により,PDGFRの過剰発現と異常なPDGFRシグナル伝達が生じます.
- LRP1の欠乏は,弾性層の破壊,SMCの増殖,動脈瘤の形成,動脈硬化への感受性の増加につながる.
- Gleevec治療は,観察された血管異常を緩和しました.
結論:
- LRP1は,血管壁の整合性を維持する上で重要な役割を果たします.
- LRP1はPDGFRの活性化とシグナル伝達を制御することによって,動脈硬化症を予防します.
- LRP1-PDGFRの相互作用をターゲットにすることで,動脈硬化症の治療戦略を提供することができる.
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