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Cardiovasc Res. 2014 Nov 1;104(2):258-69. doi: 10.1093/cvr/cvu205. Epub 2014 Sep 10.

Study familial hypertrophic cardiomyopathy using patient-specific induced pluripotent stem cells.

Author information

1
Department of Developmental Biology, University of Pittsburgh School of Medicine, 8117 Rangos Research Center, 530 45th Street, Pittsburgh, PA 15201, USA.
2
Center for Cellular and Systems Electrophysiology, Department of Physiology and Biophysics, SUNY, Buffalo, NY 14214, USA.
3
Department of Internal Medicine, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
4
Department of Obstetrics and Gynecology, SUNY, Buffalo, NY 14214, USA.
5
Department of Developmental Biology, University of Pittsburgh School of Medicine, 8117 Rangos Research Center, 530 45th Street, Pittsburgh, PA 15201, USA lyang@pitt.edu.

Abstract

AIMS:

Familial hypertrophic cardiomyopathy (HCM) is one the most common heart disorders, with gene mutations in the cardiac sarcomere. Studying HCM with patient-specific induced pluripotent stem-cell (iPSC)-derived cardiomyocytes (CMs) would benefit the understanding of HCM mechanism, as well as the development of personalized therapeutic strategies.

METHODS AND RESULTS:

To investigate the molecular mechanism underlying the abnormal CM functions in HCM, we derived iPSCs from an HCM patient with a single missense mutation (Arginine442Glycine) in the MYH7 gene. CMs were next enriched from HCM and healthy iPSCs, followed with whole transcriptome sequencing and pathway enrichment analysis. A widespread increase of genes responsible for 'Cell Proliferation' was observed in HCM iPSC-CMs when compared with control iPSC-CMs. Additionally, HCM iPSC-CMs exhibited disorganized sarcomeres and electrophysiological irregularities. Furthermore, disease phenotypes of HCM iPSC-CMs were attenuated with pharmaceutical treatments.

CONCLUSION:

Overall, this study explored the possible patient-specific and mutation-specific disease mechanism of HCM, and demonstrates the potential of using HCM iPSC-CMs for future development of therapeutic strategies. Additionally, the whole methodology established in this study could be utilized to study mechanisms of other human-inherited heart diseases.

KEYWORDS:

Cardiomyocyte; Heart; Hypertrophic cardiomyopathy; Induced pluripotent stem cells

PMID:
25209314
PMCID:
PMC4217687
DOI:
10.1093/cvr/cvu205
[Indexed for MEDLINE]
Free PMC Article

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