人間の冠動脈と大動脈動脈硬化症のプロテオミック構造

David M Herrington¹, Chunhong Mao², Sarah J Parker³

¹Section on Cardiovascular Medicine, Department of Internal Medicine (D.M.H., C.F.Z., G.S.) dherring@wakehealth.edu.

Circulation

|June 20, 2018

まとめ

動脈硬化症の早期発見は個別化された心臓病予防の鍵ですこの研究は動脈タンパク質ネットワークの変化を明らかにし,冠動脈動脈硬化症を予測するプラズマバイオマーカーを特定します.

科学分野:

プロテオミクス
心血管疾患の研究
バイオマーカーの発見

背景:

動脈硬化症の早期発見は,冠動脈疾患 (CHD) の予防に不可欠です.
早期動脈硬化における動脈タンパク質のネットワークを理解することで新しいバイオマーカーと治療目標が得られます

研究の目的:

人間の動脈プロテオームを特徴づけ,早期動脈硬化に関連するプロテオーム特性を特定する.
動脈硬化症の早期発見とリスクの階層化のための新しいバイオマーカーを発見する.

主な方法:

100人の若者の冠動脈と大動脈のサンプルを分析した.
混合物の凸分析,微分依存ネットワークモデリング,および生物情報分析が採用されました.
プラズマのバイオマーカーを検証するために,プロテオミクデータを別のコホートからの臨床データと相関させました.

主要な成果:

冠動脈組織と大動脈組織,動脈硬化組織と正常組織の間では,ミトコンドリアタンパク質の豊富さの有意な違いが観察されました.
腫瘍死滅因子 (TNF) と核受容体 (PPARα,PPARγ) タンパク質ネットワークの大きな変化が早期動脈硬化で確認されました.
組織タンパク質バイオマーカーのサブセットは,プラズマで測定すると,高い精度で冠動脈動脈硬化症 (AUC=0. 92) を予測した.

結論:

人間の動脈タンパク質は解剖学的な位置と動脈硬化によって影響を受ける複雑なネットワークです
初期の動脈硬化症は,ミトコンドリアのタンパク質の量減少と特定のネットワークの変化によって特徴付けられます.
組織プロテオミクスから得られたプラズマタンパク質バイオマーカーは,冠動脈動脈硬化症を効果的に予測できます.

キーワード:

動脈硬化症バイオマーカーミトコンドリアプロテオミクス

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