太心率诱导的代谢重新连接作为收缩功能障碍的驱动因素
Chengyi Tu1, Arianne Caudal1, Yu Liu1
1Stanford Cardiovascular Institute, Stanford University, Stanford, CA, USA.
Nature biomedical engineering
|November 27, 2023
概括
长时间的低心率可以通过改变细胞代谢引起心力衰竭,导致组织缺氧和功能障碍. 补充NAD+可以恢复新陈代谢平衡,改善心脏组织的恢复.
科学领域:
- 心脏病学 心脏病学
- 代谢研究的研究.
- 生物化学 生物化学
背景情况:
- 长期高心率是心血管发病率和死亡率的危险因素.
- 即使没有先前存在的结构性心脏病,心跳动也会诱导心肌病.
研究的目的:
- 为了研究心动减速症诱导心肌病的机制.
- 为了确定代谢变化驱动在动脉动期间收缩功能障碍.
主要方法:
- 利用了人类患者的数据,狗的心动减速模型,以及来自人类诱导的多能干细胞的工程心脏组织.
- 分析了包括组织缺氧,葡萄糖利用和氧化酸化抑制在内的代谢变化.
- 评估了尼古丁胺胺氨基二核酸 (NAD) 氧化还原平衡和蛋白质乙化,特别是质细胞/内质细胞网膜Ca2+-ATPase.
主要成果:
- 高心率诱导新陈代谢重新连接,其特点是增加无氧糖解,组织缺氧和抑制氧化酸化.
- 这种代谢转变破坏了NAD+氧化还原平衡,导致蛋白质乙化增加和心力衰竭的分子特征.
- 补充NAD+逆转了NAD+氧化还原干扰,减少了sarcoplasmic/endoplasmic网膜Ca2+-ATPase乙化,并加速了工程心脏组织的功能恢复.
结论:
- 代谢的重新连接,特别是NAD+氧化还原失衡和随后的蛋白质乙化,是高心率诱导心肌病的关键驱动因素.
- 恢复NAD+氧化还原平衡为心动节拍引起的心脏功能障碍提供了潜在的治疗策略.
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