補完成分C3の阻害は,アポリプロテインE3-Leidenのトランスジェニックマウスの静脈移植動脈硬化症を軽減する
A Schepers1, M R de Vries, C J van Leuven
1Gaubius Laboratory, TNO Quality of Life, Leiden, The Netherlands.
Circulation
|December 6, 2006
まとめ
補完カスケードは静脈移植の加厚化と動脈硬化に寄与し,移植不全を防ぐための治療目標として示唆されています. 補完成分C3を阻害することで,マウスモデルでの炎症と移植の加厚を減少させました.
科学分野:
- 免疫学 免疫学とは
- 血管生物学 血管生物学
- 手術研究の研究について
背景:
- 静脈移植の不全は,しばしば親密な多発性および加速性動脈硬化症によって引き起こされます.
- 炎症は,これらの病理学的プロセスの主要な原動力です.
- 静脈移植動脈硬化症における補完体の役割は,ほとんど未知のままである.
研究 の 目的:
- 静脈移植動脈硬化症の発達における補完カスケードの関与を調査する.
- 補充をターゲットにすることが静脈移植不全の治療戦略であるかどうかを判断する.
主な方法:
- 共通の動脈の静脈間接のマウスモデルが利用されました.
- 免疫ヒストロケミストリーと定量的なmRNA分析を行い,補完成分 (C1q,C3,C9) と調節タンパク質 (CD59,補完受容体関連遺伝子) を検出した.
- 補完体受容体に関連する遺伝子y-Igを用いたC3活性化への干渉と,コブラ毒因子によるC3の阻害は,治療効果を評価するために使用されました.
主要な成果:
- 静脈移植の加厚と補完成分 (C1q,C3,C9) の堆積は4週間以内に観察されました.
- C1q,C3,CD59の局所的なmRNA発現と,補完受容体に関連する遺伝子は,加厚した移植物に検出されました.
- C3活性化の阻害は,静脈移植の加厚,C3 / C9の堆積,および炎症性細胞の浸透を大幅に減少させ,同時にアポトーシスと増殖に影響を与えます.
結論:
- コンプリメントカスケードは,静脈移植の加厚に重要な役割を果たします.
- コンプリメントの活性化,特にC3をターゲットにすることで,静脈移植の失敗を防ぐための治療的アプローチとしての可能性が示されています.
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