溶解体Ca2+流调节室内心肌细胞的自动性,与心律失常风险相关
An Xie1,2, Gyeoung-Jin Kang1,2, Eun Ji Kim1,2
1Department of Medicine, University of Minnesota, 401 East River Parkway, VCRC 1st Floor, Suite 131, Minneapolis, MN 55455, USA.
PNAS nexus
|June 12, 2023
概括
溶解体通过释放 (Ca2+) 来调节心脏细胞的自动性. 向溶酶体Ca2+流可能为治疗心脏病中的心室失常症提供一种新的策略.
科学领域:
- 心血管生理学心血管生理学
- 细胞生物学 细胞生物学
- 分子心脏病学分子心脏病学
背景情况:
- 心肌细胞中的异常自动性可以引发心室节律失常,特别是在心肌缺血期间.
- 细胞器官 (包括线粒体和溶解体) 处理 (Ca2+) 在调节心脏自动性方面起着至关重要的作用.
研究的目的:
- 研究 lysosomal Ca2+流在调节心脏自动性的作用.
- 探索向 lysosomal Ca2+ 释放作为心室心律失常的治疗策略的潜力.
主要方法:
- 利用人类诱导的多能干细胞衍生心肌细胞 (hiPSC-CMs) 和3D工程心脏组织 (EHTs).
- 从心脏病发作小鼠中检查了室内心肌细胞.
- 研究了调节短暂受体潜在粘脂素通道1 (TRPML1) 和转录因子EB (TFEB) 对 lysosomal Ca2+ 处理和自动性的影响.
主要成果:
- 抑制溶酶体Ca2+循环减少了hiPSC-CMs中的自动性.
- 激活TRPML1增强了自动性,而对抗剂减少了它.
- 调节TFEB影响了溶酶体含量和自动性.
- 减少溶酶体Ca2+释放抑制了缺血性心肌细胞和EHTs中的自动性.
- 在心肌病患者中,TRPML1在心室性心力衰竭 (VT) 患者中被上调.
结论:
- 溶解体Ca2+处理是心脏自动性的重要调节器.
- 减少 lysosomal Ca2+ 释放可能是一个可行的临床方法来预防心室节律失常.
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