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Int J Cardiol. 2017 Apr 1;232:255-263. doi: 10.1016/j.ijcard.2017.01.009. Epub 2017 Jan 5.

Energy utilization of induced pluripotent stem cell-derived cardiomyocyte in Fabry disease.

Author information

1
Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
2
Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
3
Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Pharmacology, Taipei Veterans General Hospital, Taipei, Taiwan.
4
Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.
5
Graduate Institute of Cancer Biology and Center for Molecular Medicine, China Medical University and Department of Biotechnology, Asia University, Taichung, Taiwan.
6
Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.
7
Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
8
Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Chest Department, Taipei Veterans General Hospital, Taipei, Taiwan.
9
Graduate Institute of Cancer Biology and Center for Molecular Medicine, China Medical University and Department of Biotechnology, Asia University, Taichung, Taiwan; Department of Emergent Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
10
University of California Irvine Diabetes Center and Department of Medicine, Irvine, CA 92697, United States.
11
Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Pediatrics, Taipei Veterans General Hospital, Taipei, Taiwan.
12
Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.
13
Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.
14
Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan. Electronic address: shchiou@vghtpe.gov.tw.
15
Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Heath Care and Management Center, Taipei Veterans General Hospital, Taipei, Taiwan; Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan. Electronic address: hbleu@vghtpe.gov.tw.

Abstract

BACKGROUND:

Fabry disease (FD) is a lysosomal storage disease in which glycosphingolipids (GB3) accumulate in organs of the human body, leading to idiopathic hypertrophic cardiomyopathy and target organ damage. Its pathophysiology is still poorly understood.

OBJECTIVES:

We aimed to generate patient-specific induced pluripotent stem cells (iPSC) from FD patients presenting cardiomyopathy to determine whether the model could recapitulate key features of the disease phenotype and to investigate the energy metabolism in Fabry disease.

METHODS:

Peripheral blood mononuclear cells from a 30-year-old Chinese man with a diagnosis of Fabry disease, GLA gene (IVS4+919G>A) mutation were reprogrammed into iPSCs and differentiated into iPSC-CMs and energy metabolism was analyzed in iPSC-CMs.

RESULTS:

The FD-iPSC-CMs recapitulated numerous aspects of the FD phenotype including reduced GLA activity, cellular hypertrophy, GB3 accumulation and impaired contractility. Decreased energy metabolism with energy utilization shift to glycolysis was observed, but the decreased energy metabolism was not modified by enzyme rescue replacement (ERT) in FD-iPSCs-CMs.

CONCLUSION:

This model provided a promising in vitro model for the investigation of the underlying disease mechanism and development of novel therapeutic strategies for FD. This potential remedy for enhancing the energetic network and utility efficiency warrants further study to identify novel therapies for the disease.

PMID:
28082092
DOI:
10.1016/j.ijcard.2017.01.009
[Indexed for MEDLINE]

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