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心血管疾患における組織因子:分子機構と臨床的影響
Jan Steffel1, Thomas F Lüscher, Felix C Tanner
1Cardiovascular Research, Physiology Institute, Center for Integrative Human Physiology, University of Zürich, Zürich, Switzerland.
Circulation
|February 8, 2006
まとめ
組織因子 (TF) は血液の凝固を開始し,心血管疾患に関連しています. TFを阻害することは,これらの状態を治療するための有望な治療戦略を提供します.
科学分野:
- バイオケミストリー バイオケミストリー
- 血管生物学 血管生物学
- 心血管医学 心血管医学
背景:
- 組織因子 (TF) は凝固カスケードの主要なイニシアターであり,因子VIIaを結合させ因子IXとXを活性化させ,繊維素の形成につながります.
- TF発現は,MAPキナーゼやPI3キナーゼのようなシグナル伝達経路を通じた様々な刺激によって,内皮細胞,滑らかな筋肉細胞,単細胞で誘導される.
- 細胞TFは表面,暗号化,および細胞内プールに存在し,循環するTFは血流でも検出できます.
研究 の 目的:
- 組織因子 (TF) が凝固と心血管疾患の病原性における役割を検討する.
- TFのシグナル伝達メカニズムとセルラープールを探求する.
- 心血管疾患の治療のためのTFを標的とした治療戦略について議論する.
主な方法:
- 凝固と心血管疾患におけるTFの役割に関する文献レビュー.
- TF表現,活動,シグナル伝達経路の分析.
- TFを対象とした治療的介入の検討.
主要な成果:
- 高濃度のTFは,心血管の危険因子 (高血圧,糖尿病,脂質不全,喫煙) および急性冠動脈症候群と関連しています.
- TFは,血栓形成と血管の滑らかな筋肉細胞の移動/増殖を促進することによって,動脈硬化に寄与します.
- 治療戦略には,抗TF抗体,改変因子VIIa,およびTF経路阻害剤が含まれています.
結論:
- TFは凝固の重要なイニシアターであり,心血管疾患の病原性における重要な要因です.
- ターゲティングTFアクションは,心血管疾患に対する有望な治療の道を示しています.
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