BRD4作为心房纤维化和心房的治疗标
Shuai Song1, Jiali Yuan1, Guojian Fang1
1Department of Cardiology, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, 200092, China.
含有基多马因的蛋白4 (BRD4) 通过促进心房纤维细胞的增殖和细胞外基质合成来驱动心房动. 抑制BRD4为这种情况提供了潜在的向治疗.
科学领域:
- 心血管生物学 心血管生物学
- 分子医学是分子医学.
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 心房动 (AF) 是一种与心房重塑相关的常见心律失常.
- 特定分子机制的作用,如BRD4,在AF的发病过程中仍然不完全理解.
研究的目的:
- 研究BRD4在心房动中的作用背后的分子机制.
- 评估BRD4作为AF的潜在治疗点.
主要方法:
- 分析BRD4表达在人类AF心房和小鼠心房纤维化模型中的表达.
- 使用JQ1对BRD4进行药理抑制,并在心房纤维细胞 (aFB) 和小鼠中进行基因切除.
- RNA测序 (RNA-seq) 和染色体免疫沉测序 (ChIP-seq) 用于识别BRD4标.
- 在体内评估心房纤维化,心房扩大和AF易感性.
主要成果:
- 在AF患者中,BRD4表达上调,并与心房纤维化和aFB分化有关.
- 在aFBs中,BRD4抑制 (JQ1或shRNA) 抑制了ANG-II诱导的细胞外基质生成和细胞循环进展.
- BRD4的向是与生殖和生殖相关的基因.
- 在体内BRD4抑制或淘汰赛减弱了AF相关的心房重塑和敏感性.
结论:
- BRD4是病理性AF的关键调解者,通过促进aFB的增殖和细胞外矩阵合成.
- 向BRD4为AF治疗提供了一个有前途的治疗策略.
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