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Human-induced pluripotent stem cells for modelling metabolic perturbations and impaired bioenergetics underlying cardiomyopathies.
- Source :
-
Cardiovascular research [Cardiovasc Res] 2021 Feb 22; Vol. 117 (3), pp. 694-711. - Publication Year :
- 2021
-
Abstract
- Normal cardiac contractile and relaxation functions are critically dependent on a continuous energy supply. Accordingly, metabolic perturbations and impaired mitochondrial bioenergetics with subsequent disruption of ATP production underpin a wide variety of cardiac diseases, including diabetic cardiomyopathy, dilated cardiomyopathy, hypertrophic cardiomyopathy, anthracycline cardiomyopathy, peripartum cardiomyopathy, and mitochondrial cardiomyopathies. Crucially, there are no specific treatments for preventing the onset or progression of these cardiomyopathies to heart failure, one of the leading causes of death and disability worldwide. Therefore, new treatments are needed to target the metabolic disturbances and impaired mitochondrial bioenergetics underlying these cardiomyopathies in order to improve health outcomes in these patients. However, investigation of the underlying mechanisms and the identification of novel therapeutic targets have been hampered by the lack of appropriate animal disease models. Furthermore, interspecies variation precludes the use of animal models for studying certain disorders, whereas patient-derived primary cell lines have limited lifespan and availability. Fortunately, the discovery of human-induced pluripotent stem cells has provided a promising tool for modelling cardiomyopathies via human heart tissue in a dish. In this review article, we highlight the use of patient-derived iPSCs for studying the pathogenesis underlying cardiomyopathies associated with metabolic perturbations and impaired mitochondrial bioenergetics, as the ability of iPSCs for self-renewal and differentiation makes them an ideal platform for investigating disease pathogenesis in a controlled in vitro environment. Continuing progress will help elucidate novel mechanistic pathways, and discover novel therapies for preventing the onset and progression of heart failure, thereby advancing a new era of personalized therapeutics for improving health outcomes in patients with cardiomyopathy.<br /> (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)
- Subjects :
- Anthracyclines toxicity
Cardiomyopathies chemically induced
Cardiomyopathies genetics
Cardiomyopathies pathology
Cardiomyopathy, Dilated genetics
Cardiomyopathy, Dilated metabolism
Cardiomyopathy, Dilated pathology
Cardiomyopathy, Hypertrophic genetics
Cardiomyopathy, Hypertrophic metabolism
Cardiomyopathy, Hypertrophic pathology
Cardiotoxicity
Cell Differentiation
Cell Proliferation
Cells, Cultured
Diabetic Cardiomyopathies genetics
Diabetic Cardiomyopathies metabolism
Diabetic Cardiomyopathies pathology
Female
Gene Expression Regulation
Humans
Induced Pluripotent Stem Cells pathology
Mitochondria, Heart pathology
Myocytes, Cardiac pathology
Peripartum Period
Phenotype
Pregnancy
Pregnancy Complications, Cardiovascular genetics
Pregnancy Complications, Cardiovascular metabolism
Pregnancy Complications, Cardiovascular pathology
Cardiomyopathies metabolism
Energy Metabolism
Induced Pluripotent Stem Cells metabolism
Mitochondria, Heart metabolism
Myocytes, Cardiac metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1755-3245
- Volume :
- 117
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Cardiovascular research
- Publication Type :
- Academic Journal
- Accession number :
- 32365198
- Full Text :
- https://doi.org/10.1093/cvr/cvaa125