线粒体
心肌保护
移植
心肌细胞
收缩性
心力衰竭
生物
细胞生物学
心脏移植
心功能曲线
药理学
内科学
医学
内分泌学
心肌梗塞
作者
Alian Zhang,Yangyang Liu,Jianan Pan,Francesca Pontanari,Andrew Chia-Hao Chang,Honghui Wang,Shuang Gao,Changqian Wang,Alex CY. Chang
标识
DOI:10.1016/j.ymthe.2023.02.016
摘要
Mitochondrial dysfunction is a hallmark of heart failure. Mitochondrial transplantation has been demonstrated to be able to restore heart function, but its mechanism of action remains unresolved. Using an in-house optimized mitochondrial isolation method, we tested efficacy of mitochondria transplantation in two different heart failure models. First, using a doxorubicin-induced heart failure model, we demonstrate that mitochondrial transplantation before doxorubicin challenge protects cardiac function in vivo and prevents myocardial apoptosis, but contraction improvement relies on the metabolic compatibility between transplanted mitochondria and treated cardiomyocytes. Second, using a mutation-driven dilated cardiomyopathic human induced pluripotent stem cell-derived cardiomyocyte model, we demonstrate that mitochondrial transplantation preferentially boosts contraction in the ventricular myocytes. Last, using single-cell RNA-seq, we show that mitochondria transplantation boosts contractility in dystrophic cardiomyocytes with few transcriptomic alterations. Together, we provide evidence that mitochondria transplantation confers myocardial protection and may serve as a potential therapeutic option for heart failure.
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