心脏压力过载降低左心室ETV1表达,有助于心室电气和结构重塑
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
概括
在心力衰竭期间,ETV1 (ETS转位变异1) 在左心室下降,导致心室重塑和心律失常. 这项研究研究了ETV1
科学领域:
- 心脏病学
- 分子生物学
- 遗传学
背景情况:
- 由心力衰竭引起的压力过重会导致左心房重塑,导致肌肉病和心律失常.
- 在心脏压力过载中驱动心房重塑的分子途径尚不清楚.
研究的目的:
- 在心脏压力过载时描述ETV1 (ETS转位变异1) 信号轴响应.
- 探索ETV1在心房电气和结构改造中的作用.
主要方法:
- 265个人类LA样本和两种小鼠压力过载模型的基因表达概况 (横向大动脉收缩,血管素II输注).
- 使用心肌细胞特异性淘汰小鼠模型 (Etv1^Mlc2a) 来研究Etv1的功能.
主要成果:
- 人类LA样本中的ETV1表达率下降,这些样本来自减少喷射分数的患者和小鼠压力过载模型.
- ETV1的表达与参与快速传导 (NRG1,ERBB4,SCN5A,GJA5) 的基因相关,并且在压力过载时与这些基因一起下调.
- Etv1 淘汰的小鼠表现出心房传导疾病,心律失常以及基因表达的改变,这与传导障碍和纤维化变化一致.
结论:
- 在心脏压力过载时,ETV1在LA下调.
- 减少ETV1有助于左心室的电气和结构重塑,促进心律失常.
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