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The intracellular Ca2+ concentration is elevated in cardiomyocytes differentiated from hiPSCs derived from a Duchenne muscular dystrophy patient.
PLoS One. 2019; 14(3):e0213768.Plos

Abstract

Duchenne muscular dystrophy (DMD) is the most common and severe form of muscular dystrophy. The major symptoms of this condition are walking difficulties, dyspnea caused by progressive skeletal muscle weakness, and cardiomyopathy. Recent advances in ventilator support devices have dramatically decreased mortality caused by respiratory distress. Consequently, cardiomyopathy resulting in heart failure is currently the major cause of death among DMD patients. One mechanism by which skeletal muscle is damaged in DMD patients involves elevation of the intracellular Ca2+ concentration. By contrast, the mechanisms underlying the development of cardiomyopathy are unclear. To investigate this, we examined the intracellular Ca2+ concentration and calcium transients in cardiomyocytes differentiated from human induced pluripotent stem cells (hiPSCs). hiPSCs were derived from a DMD patient (DMD-hiPSCs), in whom exon 44 of the gene encoding dystrophin was deleted, and from his parents (control-hiPSCs), who did not carry this mutation. The intracellular Ca2+ concentration was measured using the fluorescent indicator indo-1. The fluorescence ratio (410/490 nm) of indo-1 at rest (R0), the peak of this ratio (Rmax), and the amplitude (Rmax-R0) were significantly higher in cardiomyocytes differentiated from DMD-hiPSCs than in those differentiated from control-hiPSCs. Moreover, mechanical stretching significantly increased the intracellular Ca2+ concentration in cardiomyocytes differentiated from DMD-hiPSCs, but not in those differentiated from control-hiPSCs. These findings indicate that elevation of the intracellular Ca2+ concentration can cause cardiac damage leading to cardiomyopathy in DMD patients.

Authors+Show Affiliations

Department of Pediatrics, Graduate School of Medicine Kyoto University, Kyoto City, Japan.Department of Pediatrics, Graduate School of Medicine Kyoto University, Kyoto City, Japan.Department of Pediatrics, Graduate School of Medicine Kyoto University, Kyoto City, Japan.Department of Pediatrics, Graduate School of Medicine Kyoto University, Kyoto City, Japan.Department of Pediatrics, Graduate School of Medicine Kyoto University, Kyoto City, Japan.Department of Pediatrics, Graduate School of Medicine Kyoto University, Kyoto City, Japan.Department of Pediatrics, Graduate School of Medicine Kyoto University, Kyoto City, Japan.

Pub Type(s)

Case Reports
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30875388

Citation

Tsurumi, Fumitoshi, et al. "The Intracellular Ca2+ Concentration Is Elevated in Cardiomyocytes Differentiated From hiPSCs Derived From a Duchenne Muscular Dystrophy Patient." PloS One, vol. 14, no. 3, 2019, pp. e0213768.
Tsurumi F, Baba S, Yoshinaga D, et al. The intracellular Ca2+ concentration is elevated in cardiomyocytes differentiated from hiPSCs derived from a Duchenne muscular dystrophy patient. PLoS ONE. 2019;14(3):e0213768.
Tsurumi, F., Baba, S., Yoshinaga, D., Umeda, K., Hirata, T., Takita, J., & Heike, T. (2019). The intracellular Ca2+ concentration is elevated in cardiomyocytes differentiated from hiPSCs derived from a Duchenne muscular dystrophy patient. PloS One, 14(3), e0213768. https://doi.org/10.1371/journal.pone.0213768
Tsurumi F, et al. The Intracellular Ca2+ Concentration Is Elevated in Cardiomyocytes Differentiated From hiPSCs Derived From a Duchenne Muscular Dystrophy Patient. PLoS ONE. 2019;14(3):e0213768. PubMed PMID: 30875388.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The intracellular Ca2+ concentration is elevated in cardiomyocytes differentiated from hiPSCs derived from a Duchenne muscular dystrophy patient. AU - Tsurumi,Fumitoshi, AU - Baba,Shiro, AU - Yoshinaga,Daisuke, AU - Umeda,Katsutsugu, AU - Hirata,Takuya, AU - Takita,Junko, AU - Heike,Toshio, Y1 - 2019/03/15/ PY - 2018/06/20/received PY - 2019/03/01/accepted PY - 2019/3/16/entrez PY - 2019/3/16/pubmed PY - 2019/3/16/medline SP - e0213768 EP - e0213768 JF - PloS one JO - PLoS ONE VL - 14 IS - 3 N2 - Duchenne muscular dystrophy (DMD) is the most common and severe form of muscular dystrophy. The major symptoms of this condition are walking difficulties, dyspnea caused by progressive skeletal muscle weakness, and cardiomyopathy. Recent advances in ventilator support devices have dramatically decreased mortality caused by respiratory distress. Consequently, cardiomyopathy resulting in heart failure is currently the major cause of death among DMD patients. One mechanism by which skeletal muscle is damaged in DMD patients involves elevation of the intracellular Ca2+ concentration. By contrast, the mechanisms underlying the development of cardiomyopathy are unclear. To investigate this, we examined the intracellular Ca2+ concentration and calcium transients in cardiomyocytes differentiated from human induced pluripotent stem cells (hiPSCs). hiPSCs were derived from a DMD patient (DMD-hiPSCs), in whom exon 44 of the gene encoding dystrophin was deleted, and from his parents (control-hiPSCs), who did not carry this mutation. The intracellular Ca2+ concentration was measured using the fluorescent indicator indo-1. The fluorescence ratio (410/490 nm) of indo-1 at rest (R0), the peak of this ratio (Rmax), and the amplitude (Rmax-R0) were significantly higher in cardiomyocytes differentiated from DMD-hiPSCs than in those differentiated from control-hiPSCs. Moreover, mechanical stretching significantly increased the intracellular Ca2+ concentration in cardiomyocytes differentiated from DMD-hiPSCs, but not in those differentiated from control-hiPSCs. These findings indicate that elevation of the intracellular Ca2+ concentration can cause cardiac damage leading to cardiomyopathy in DMD patients. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/30875388/The_intracellular_Ca2+_concentration_is_elevated_in_cardiomyocytes_differentiated_from_hiPSCs_derived_from_a_Duchenne_muscular_dystrophy_patient_ L2 - http://dx.plos.org/10.1371/journal.pone.0213768 DB - PRIME DP - Unbound Medicine ER -