Genetic Cardiomyopathies: The Lesson Learned from hiPSCs
Genetic cardiomyopathies represent a wide spectrum of inherited diseases and constitute an important cause of morbidity and mortality among young people, which can manifest with heart failure, arrhythmias, and/or sudden cardiac death. Multiple underlying genetic variants and molecular pathways have...
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doaj-85622fef5d2c4b2d884e1167b70912832021-03-10T00:07:05ZengMDPI AGJournal of Clinical Medicine2077-03832021-03-01101149114910.3390/jcm10051149Genetic Cardiomyopathies: The Lesson Learned from hiPSCsIlaria My0Elisa Di Di Di Pasquale1Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20090 Milan, ItalyHumanitas Clinical and Research Center—IRCCS, Rozzano, 20089 Milan, ItalyGenetic cardiomyopathies represent a wide spectrum of inherited diseases and constitute an important cause of morbidity and mortality among young people, which can manifest with heart failure, arrhythmias, and/or sudden cardiac death. Multiple underlying genetic variants and molecular pathways have been discovered in recent years; however, assessing the pathogenicity of new variants often needs in-depth characterization in order to ascertain a causal role in the disease. The application of human induced pluripotent stem cells has greatly helped to advance our knowledge in this field and enabled to obtain numerous in vitro patient-specific cellular models useful to study the underlying molecular mechanisms and test new therapeutic strategies. A milestone in the research of genetically determined heart disease was the introduction of genomic technologies that provided unparalleled opportunities to explore the genetic architecture of cardiomyopathies, thanks to the generation of isogenic pairs. The aim of this review is to provide an overview of the main research that helped elucidate the pathophysiology of the most common genetic cardiomyopathies: hypertrophic, dilated, arrhythmogenic, and left ventricular noncompaction cardiomyopathies. A special focus is provided on the application of gene-editing techniques in understanding key disease characteristics and on the therapeutic approaches that have been tested.https://www.mdpi.com/2077-0383/10/5/1149genetic cardiomyopathiesinduced pluripotent stem cellsCRISPR/Cas9gene editinghypertrophic cardiomyopathydilated cardiomyopathy |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ilaria My Elisa Di Di Di Pasquale |
spellingShingle |
Ilaria My Elisa Di Di Di Pasquale Genetic Cardiomyopathies: The Lesson Learned from hiPSCs Journal of Clinical Medicine genetic cardiomyopathies induced pluripotent stem cells CRISPR/Cas9 gene editing hypertrophic cardiomyopathy dilated cardiomyopathy |
author_facet |
Ilaria My Elisa Di Di Di Pasquale |
author_sort |
Ilaria My |
title |
Genetic Cardiomyopathies: The Lesson Learned from hiPSCs |
title_short |
Genetic Cardiomyopathies: The Lesson Learned from hiPSCs |
title_full |
Genetic Cardiomyopathies: The Lesson Learned from hiPSCs |
title_fullStr |
Genetic Cardiomyopathies: The Lesson Learned from hiPSCs |
title_full_unstemmed |
Genetic Cardiomyopathies: The Lesson Learned from hiPSCs |
title_sort |
genetic cardiomyopathies: the lesson learned from hipscs |
publisher |
MDPI AG |
series |
Journal of Clinical Medicine |
issn |
2077-0383 |
publishDate |
2021-03-01 |
description |
Genetic cardiomyopathies represent a wide spectrum of inherited diseases and constitute an important cause of morbidity and mortality among young people, which can manifest with heart failure, arrhythmias, and/or sudden cardiac death. Multiple underlying genetic variants and molecular pathways have been discovered in recent years; however, assessing the pathogenicity of new variants often needs in-depth characterization in order to ascertain a causal role in the disease. The application of human induced pluripotent stem cells has greatly helped to advance our knowledge in this field and enabled to obtain numerous in vitro patient-specific cellular models useful to study the underlying molecular mechanisms and test new therapeutic strategies. A milestone in the research of genetically determined heart disease was the introduction of genomic technologies that provided unparalleled opportunities to explore the genetic architecture of cardiomyopathies, thanks to the generation of isogenic pairs. The aim of this review is to provide an overview of the main research that helped elucidate the pathophysiology of the most common genetic cardiomyopathies: hypertrophic, dilated, arrhythmogenic, and left ventricular noncompaction cardiomyopathies. A special focus is provided on the application of gene-editing techniques in understanding key disease characteristics and on the therapeutic approaches that have been tested. |
topic |
genetic cardiomyopathies induced pluripotent stem cells CRISPR/Cas9 gene editing hypertrophic cardiomyopathy dilated cardiomyopathy |
url |
https://www.mdpi.com/2077-0383/10/5/1149 |
work_keys_str_mv |
AT ilariamy geneticcardiomyopathiesthelessonlearnedfromhipscs AT elisadididipasquale geneticcardiomyopathiesthelessonlearnedfromhipscs |
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