减少的TBX5-依赖基因调节网络将心房动与心力衰竭联系在一起
Sonja Lazarevic1, Carlos Perez-Cervantes1, Zhezhen Wang1
1Department of Pediatrics, Pathology, and Human Genetics, University of Chicago, Chicago, IL, USA.
Nature cardiovascular research
|February 23, 2026
概括
心房动 (AF) 和心力衰竭 (HF) 分享了涉及破坏基因调节的分子机制. 像TBX5这样的关键转录因子被下调,这表明它们之间的联系是共同的基因组损伤反应的基础.
科学领域:
- 心血管生物学 心血管生物学
- 分子遗传学 分子遗传学
- 系统生物学 系统生物学
背景情况:
- 心房动 (AF) 和心力衰竭 (HF) 经常同时存在,加剧了患者的结果.
- 共同的分子通路可能是AF和HF之间的双向关系的基础.
研究的目的:
- 通过在AF和HF小鼠模型中比较心房基因调节网络 (GRNs) 来研究共享的分子机制.
- 在心房组织中识别常见的转录和基因组变化.
主要方法:
- 在Tbx5条件淘汰赛 (Tbx5 cKO) 小鼠 (AF模型) 和横向大动脉收缩 (TAC) 小鼠 (HF模型) 中对心房基因调控网络 (GRNs) 的比较.
- 对心房转录和基因组资料的分析,重点是转录因子基因失调.
主要成果:
- 在AF和HF模型中观察到心房转录和基因组概况的高度相关的变化.
- 在小鼠和人类中都发现了下调的心房Tbx5表达.
- 超过100个转录因子基因被协调失调,破坏了TBX5驱动的GRN,并出现了Sox9-关联网络.
结论:
- 在AF和HF中,TBX5-依赖性心房基因调节的协调中断发生.
- 一个共享的基因组损伤反应可能会导致AF和HF之间的相互风险.
- 识别这些共享机制可能会导致新的治疗策略.
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