EphA2の発現は,動脈硬化症における炎症と繊維増殖的再構成を調節する

Alexandra C Finney¹, Steven D Funk¹, Jonette M Green¹

¹From Departments of Cell Biology and Anatomy (A.C.F., S.D.F., J.M.G., A. Yurdagul, C.G.K., A.W.O.), Pathology and Translational Pathobiology (J.M.G., A. Yurdagul, R.P., M.H., J.G.T., C.G.K., A.W.O.), Cardiology (M.A.R.), Microbiology and Immunology (A. Yurochko, M.D.W.), and Molecular and Cellular Physiology (C.B.P., C.G.K., A.W.O.), Louisiana State University Health Sciences Center-Shreveport; Departments of Cancer Biology and Cell and Developmental Biology, Vanderbilt University, Nashville, TN (J.C.); and Veterans Affairs Medical Center, Tennessee Valley Healthcare System, Nashville (J.C.).

Circulation

|May 11, 2017

まとめ

EphA2 (エフリン受容体A2) は動脈硬化において重要な役割を果たし,プラークの炎症と進行に影響を与えます. EphA2を削除すると,動脈硬化性プラーク形成と進行した病変の発生が減少します.

科学分野:

心血管生物学
分子医学
免疫学

背景:

動脈硬化症は慢性的な炎症と血管壁の改造を伴う
ヒトとマウスの動脈硬化性プラークでは,EfA2の発現が上昇していることが観察されています.

研究の目的:

動脈硬化症の発達と進行におけるEphA2の役割を調査する.
EphA2 が動脈硬化性プラーク形成に影響を与える細胞メカニズムを解明する.

主な方法:

西洋の食事で餌を与えられたアポエ・マウスでエファ2ノックアウトを活用した.
動脈硬化負荷と血脂質を評価し細胞培養実験を行いました
エンドテリアのEphA2ノックダウンと骨髄キメラを使用した.

主要な成果:

EphA2-/-アポエ-/-マウスは,体重と脂質の増加にもかかわらず,プラーク形成,炎症,およびマクロファージの含有量が減少した.
内皮のEphA2のノックダウンにより単細胞の結合が低下し,血液形成の消去は効果がなかった.
EphA2の消去は滑らかな筋肉の増殖と細胞外マトリックス沈着を減少させ,進行したプラークの進行を阻害した.

結論:

EphA2は,動脈硬化性炎症と進行した病変の両方の新しい調節剤です.
内皮のEphA2は単細胞の粘着を促進し,炎症に寄与する.
滑らかな筋肉のEphA2は,増殖とマトリックス堆積を通して,高度なプラーク発育に影響を与えます.

キーワード:

動脈硬化症細胞増殖細胞外マトリックス繊維症炎症筋細胞,滑らかな筋肉

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