Cell Proliferation >

2024 , Vol. 57 >Issue 4: 0

DOI: https://doi.org/10.1111/cpr.13573

Mitochondrial dysfunction is associated with hypertrophic cardiomyopathy in Pompe disease-specific induced pluripotent stem cell-derived cardiomyocytes

  • Wenjun Huang 1 ,
  • Rui Zhou 1 ,
  • Congshan Jiang 1 ,
  • Jie Wang 1 ,
  • Yafei Zhou 1 ,
  • Xiaoyan Xu 2 ,
  • Tao Wang 2 ,
  • Anmao Li 1 ,
  • Yanmin Zhang , 1,2
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  • 1. National Regional Children's Medical Center (Northwest), Key Laboratory of Precision Medicine to Pediatric Diseases of Shaanxi Province, Xi'an Key Laboratory of Children's Health and Diseases, Shaanxi Institute for Pediatric Diseases, Xi'an Children's Hospital, Affiliated Children's Hospital of Xi'an Jiaotong University, Xi'an, China
  • 2. Department of Cardiology, Xi'an Children's Hospital, Affiliated Children's Hospital of Xi'an Jiaotong University, Xi'an, China
ymzh628@126.com

Received date: 26 Dec 2022

Revised date: 21 Oct 2023

Accepted date: 25 Oct 2023

Copyright

2023 2023 The Authors. Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.
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Abstract

Pompe disease (PD) is a rare autosomal recessive disorder that presents with progressive hypertrophic cardiomyopathy. However, the detailed mechanism remains clarified. Herein, PD patient-specific induced pluripotent stem cells were differentiated into cardiomyocytes (PD-iCMs) that exhibited cardiomyopathic features of PD, including decreased acid alpha-glucosidase activity, lysosomal glycogen accumulation and hypertrophy. The defective mitochondria were involved in the cardiac pathology as shown by the significantly decreased number of mitochondria and impaired respiratory function and ATP production in PD-iCMs, which was partially due to elevated levels of intracellular reactive oxygen species produced from depolarized mitochondria. Further analysis showed that impaired fusion and autophagy of mitochondria and declined expression of mitochondrial complexes underlies the mechanism of dysfunctional mitochondria. This was alleviated by supplementation with recombinant human acid alpha-glucosidase that improved the mitochondrial function and concomitantly mitigated the cardiac pathology. Therefore, this study suggests that defective mitochondria underlie the pathogenesis of cardiomyopathy in patients with PD.

Cite this article

Wenjun Huang , Rui Zhou , Congshan Jiang , Jie Wang , Yafei Zhou , Xiaoyan Xu , Tao Wang , Anmao Li , Yanmin Zhang . Mitochondrial dysfunction is associated with hypertrophic cardiomyopathy in Pompe disease-specific induced pluripotent stem cell-derived cardiomyocytes[J]. Cell Proliferation, 2024 , 57(4) : e13573 . DOI: 10.1111/cpr.13573

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