内皮C型ナトリウレチンペプチドは血管新生と血管再構成の重要な調節剤である

Kristen J Bubb^1,2, Aisah A Aubdool¹, Amie J Moyes¹

¹William Harvey Research Institute, Barts & The London School of Medicine & Dentistry, Queen Mary University of London, UK (K.J.B., A.A.A., A.J.M., J.P.D., A.J.H.).

Circulation

|December 28, 2018

まとめ

C型ナトリウレチンペプチド (CNP) は,不血症後の血管修復に不可欠です. その受容体であるNPR-Cを活性化することで血管新生と血管再建が促進され心血管疾患の新たな治療戦略が提供されます

科学分野:

心血管生物学
内皮細胞生物学
分子医学

背景:

血管新生と血管再構築は心血管不全に伴う重要な先天的な反応です
内皮は血液供給と酸素供給の回復に重要な役割を果たします
C型ナトリウレチンペプチド (CNP) は,血管ホメオスタシスを調節する重要な内皮信号分子である.

研究の目的:

血管新生と血管再建における CNP の中心的な役割を調査する.
内皮細胞と体内のモデルにおける CNP とその受容体の機能を調査する.
周辺動脈疾患の患者における CNP/NPR-C発現を検査する.

主な方法:

様々なノックアウトマウスモデルからの内皮細胞と大動脈のリングを用いた試験.
血管新生や血管損傷後の血管再建のインビボ評価
患者の組織におけるCNPとNPR-C発現の分析

主要な成果:

CNPとNPR- Cの低下は,臨床的血管不全と関連しています.
CNPまたはNPR- Cの抑制は,ex vivoおよびin vivoの血管新生および再構成を阻害する.
CNP/NPR-Cのプロ血管新生作用には,Gi,ERK1/2,PI3Kγ/Aktの信号伝達経路が関与する.
薬学的なCNP投与は,CNP欠乏症のモデルにおける損傷した血管新生を救済する.

結論:

CNPは,イシュケミア誘発の血管新生および血管再構成において中心的な病理学的役割を果たします.
NPR-Cの活性化は,外周動脈疾患と血栓性疾患の潜在的治療標的である.

キーワード:

エンドセリウムイシュミアナトリウレティックペプチド,C型新血管化,生理学的外周動脈疾患血管の改造

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