心圧過負荷は左心房におけるETV1の発現を低下させ,心房の電気的および構造的改造に貢献する

Naoko Yamaguchi¹, Junhua Xiao¹, Deven Narke¹

¹The Leon H. Charney Division of Cardiology (N.Y., J.X., D.N., D.S., X.L., E.O., A.S., D.S.P.), New York University Grossman School of Medicine.

Circulation

|November 23, 2020

まとめ

ETV1 (ETSトランスロケーション変種1) は心不全時に左心房に減少し,心房の改造と不律に寄与する. この研究は,ETV1を調査しています.

科学分野:

心臓病科
分子生物学
遺伝学

背景:

心不全による圧力過負荷は左心房 (LA) の改造を引き起こし,心筋不全と不律を引き起こします.
心圧過負荷における心房改造を誘発する分子経路は十分に理解されていません.

研究の目的:

心圧過負荷時のLAにおけるETV1 (ETSトランスロケーション変種1) 信号軸応答を特徴づける.
心房の電気的および構造的改造における ETV1 の役割を調査する.

主な方法:

265人のLAサンプルと2つのネズミの圧力過負荷モデル (横動脈収縮,アンジオテンシンII注入) の遺伝子表現プロファイリング.
Etv1機能を研究するために,心筋細胞特異的なノックアウトマウスモデル (Etv1^Mlc2a) を利用した.

主要な成果:

ETV1の発現は,エジェクション分子が低下したヒトのLAサンプルとマウスの圧力過負荷モデルで減少しています.
ETV1の発現は,急速伝導に関わる遺伝子 (NRG1,ERBB4,SCN5A,GJA5) と相関し,圧力の過負荷でこれらの遺伝子と共にダウンレギュレーションされる.
Etv1ノックアウトマウスは,心房伝導障害,心律乱れ,伝導障害とプロフィブロティック変化に一致する変異遺伝子発現を示した.

結論:

ETV1は,心圧過負荷時にLAでダウンレギュレーションされます.
減少したETV1は左心房の電気的および構造的な改造に寄与し,不律を促します.

キーワード:

心房細動心房の改造心不全信号変換転写因子

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