内皮細胞は,VEGFR2媒介のパラクリンシグナル伝達により,生理学的心筋細胞の成長を調節する

Riikka Kivelä¹, Karthik Amudhala Hemanthakumar¹, Katri Vaparanta^2,3

¹Wihuri Research Institute, Helsinki, Finland and Translational Cancer Biology Program, Research Programs Unit, Faculty of Medicine, University of Helsinki, Finland (R.K., K.A.H., M.R., K.A.).

Circulation

|March 30, 2019

まとめ

内皮細胞と心筋細胞は信号伝達経路を介して通信し,生理的な心臓の成長と高縮を調整する. 心臓の機能を維持するために重要なものです

科学分野:

心血管生物学
細胞シグナリング
血管新生の研究

背景:

心不全は世界の主要な健康問題であり,しばしば病的な心縮が先行する.
心血管の膨張は,生理学的対病理的な心臓の成長を決定するために重要です.
内皮細胞 (EC) と心筋細胞 (CMC) の交差は心臓の成長を調節するが,そのメカニズムは不明である.

研究の目的:

心臓の成長におけるEC-CMC相互作用のメカニズムを解明する.
CMCホメオスタシスを調節するEC由来信号を特定する.
血管新生が心筋縮にどのように影響するかを理解し,心不全の治療標的を特定する.

主な方法:

VEGF受容体を削除するためにマウスの遺伝子モデルを使用しました
心筋転移のためにアデノ関連ウイルスベクターを使用した.
細胞培養実験と分子分析 (qPCR,マイクロアレイ,ELISA,IHC) を実施した.

主要な成果:

VEGFR1とVEGFR1リガンドのECデレーションにより,冠動脈血管が増加し,生理学的CMC高縮が引き起こされた.
VEGFR2の阻害によって阻害され,内皮VEGFR2を通じたVEGFシグナリングがこれらの効果を媒介した.
ノッチとErbB経路は,EC-CMCのクロストークの主要なメディエーターとして特定されました.

結論:

EC VEGFR2とCMC ErbBのシグナル伝達経路は,CMC高縮と血管新生を調整する.
心臓の生理的な成長に寄与します
この発見は心不全の新たな治療戦略の洞察を与えてくれます

キーワード:

HB-EGF VEGF-B について VEGFR-1 について血管新生ハイパートロフィー

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