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类药物通过干扰线粒体功能和细胞内酸化来影响人类iPSC衍生的心肌细胞

Tim Somers^1,2,3, Sailay Siddiqi^1,3, Renee G C Maas⁴

¹Department of Cardiothoracic Surgery, Radboud University Medical Center, 6500 HB, Nijmegen, The Netherlands.

Basic research in cardiology

|February 2, 2024

概括

类药物可以通过损害线粒体功能和降低细胞活力来损害心肌细胞. 这项研究突出了潜在的心脏风险,特别是在患有心脏病的老年患者中.

科学领域:

心脏病学心脏病学
分子生物学分子生物学
药理学药理学是指药理学的学科.

背景情况:

类药物通过抑制胆固醇合成,有效地减少心血管事件.
类固醇诱导的肌肉疾病与线粒体功能障碍有关.
心脏功能受损的老龄化人口需要了解他类药物对心肌细胞的影响.

研究的目的:

研究常见的他类药物对人类诱导的多能干细胞衍生的心肌细胞 (hiPSC衍生的CMs) 的影响.
为了评估细胞活力,新陈代谢能力和线粒体功能后,他类药物暴露.

主要方法:

由hiPSC衍生的CMs用不同度的simvastatin,atorvastatin,rosuvastatin和cerivastatin进行治疗.
用代谢分析和光显微镜评估了细胞活力,呼吸,膜潜力和形态.

主要成果:

西姆瓦斯塔丁和阿托瓦斯塔丁显著降低了心肌细胞活力 (42-64%),并抑制了基底和最大呼吸.
西姆瓦斯塔丁乳证明了最强大的呼吸抑制作用.
线粒体膜潜力被simvastatin和atorvastatin降低.

结论:

一些他类药物,特别是simvastatin,会对心肌细胞活力和线粒体功能产生负面影响.
像阿托瓦斯酸这样的水友性他类药物对心肌细胞代谢的影响较小.
需要进一步的研究来指导临床的他类药物处方,特别是在脆弱的患者群体.

关键词:

心脏肌细胞是心脏肌细胞.线粒体中毒性线粒体中毒性类他类药物是一种药物.这是 hiPSC.

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