通过心脏素传递的副信号控制着心房纤维化和心律失常
Lucia M Moreira1, Abhijit Takawale2,3, Mohit Hulsurkar4,5
1Division of Cardiovascular Medicine, Radcliffe Department of Medicine, British Heart Foundation Centre of Research Excellence, University of Oxford, John Radcliffe Hospital, Oxford, UK.
Nature
|November 5, 2020
概括
一种甲状腺激素,由心脏细胞产生,并调节纤维化. 对于这种常见的心律失常患者来说,较低的卡尔西水平表明它可能是治疗点.
科学领域:
- 心脏病学
- 内分泌学
- 分子生物学
背景情况:
- 前庭动是一种与中风和死亡相关的常见心律失常.
- 心房纤维化是AF的关键特征, 但其分子驱动因素尚不清楚.
- 目前的AF疗法不足, 需要研究新的机制.
研究的目的:
- 研究素在心房纤维化和心房纤维化中的作用.
- 在心房肌细胞和纤维细胞中探索素的对神经信号.
- 评估人类AF患者的素水平和受体表达.
主要方法:
- 研究了心房肌细胞产生的素.
- 使用基因操纵素及其受体的小鼠模型.
- 在人类AF患者中分析了心肌素水平和纤维细胞素受体表达.
- 对人类心房纤维细胞进行了转录组和蛋白质组分析.
主要成果:
- 卡尔西因作为一个膜信号,控制纤维细胞的增殖和细胞外基质的分泌.
- 在小鼠中,全球素受体的干扰导致心房纤维化和心房纤维敏感度的增加.
- 门特异性素倒置导致纤维化和肌肉纤维化;过度表达防止了它们.
- 人类AF患者表现出显著降低的心肌和纤维细胞受体水平.
结论:
- 在预防心房纤维化和心肌纤维化方面,心肌卡尔西托尼信号传递至关重要.
- 恢复卡尔西托尼信号是一种潜在的治疗策略.
- 卡尔西的作用不仅仅是骨代谢,还包括心脏健康.
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