Modeling Catecholaminergic Polymorphic Ventricular Tachycardia using Induced Pluripotent Stem Cell-derived Cardiomyocytes
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmogenic cardiac disorder characterized by life-threatening arrhythmias induced by physical or emotional stress, in the absence structural heart abnormalities. The arrhythmias may cause syncope or degenerate into card...
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| Format: | Article |
| Language: | English |
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Rambam Health Care Campus
2012-07-01
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| Series: | Rambam Maimonides Medical Journal |
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| Online Access: | http://rmmj.org.il/Pages/ArticleHTM.aspx?manuId=224 |
| _version_ | 1811242875862646784 |
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| author | Atara Novak Avraham Lorber Joseph Itskovitz-Eldor Ofer Binah |
| author_facet | Atara Novak Avraham Lorber Joseph Itskovitz-Eldor Ofer Binah |
| author_sort | Atara Novak |
| collection | DOAJ |
| description | Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmogenic cardiac disorder characterized by life-threatening arrhythmias induced by physical or emotional stress, in the absence structural heart abnormalities. The arrhythmias may cause syncope or degenerate into cardiac arrest and sudden death which usually occurs during childhood. Recent studies have shown that CPVT is caused by mutations in the cardiac ryanodine receptor type 2 (RyR2) or calsequestrin 2 (CASQ2) genes. Both proteins are key contributors to the intracellular Ca2+ handling process and play a pivotal role in Ca2+ release from the sarcoplasmic reticulum to the cytosol during systole. Although the molecular pathogenesis of CPVT is not entirely clear, it was suggested that the CPVT mutations promote excessive sarcoplasmic reticulum Ca2+ leak, which initiates delayed afterdepolarizations (DADs) and triggered arrhythmias in cardiac myocytes. The recent breakthrough discovery of induced pluripotent stem cells (iPSC) generated from somatic cells (e.g. fibroblasts, keratinocytes) now enables researches to investigate mutated cardiomyocytes generated from the patient’s iPSC. To this end, in the present article we review recent studies on CPVT iPSC-derived cardiomyocytes, thus demonstrating in the mutated cells catecholamine-induced DADs and triggered arrhythmias. |
| first_indexed | 2024-04-12T13:58:30Z |
| format | Article |
| id | doaj.art-282665fa8df94aef925c6c7d18c03b5e |
| institution | Directory Open Access Journal |
| issn | 2076-9172 |
| language | English |
| last_indexed | 2024-04-12T13:58:30Z |
| publishDate | 2012-07-01 |
| publisher | Rambam Health Care Campus |
| record_format | Article |
| series | Rambam Maimonides Medical Journal |
| spelling | doaj.art-282665fa8df94aef925c6c7d18c03b5e2022-12-22T03:30:17ZengRambam Health Care CampusRambam Maimonides Medical Journal2076-91722012-07-0133e001510.5041/RMMJ.10086Modeling Catecholaminergic Polymorphic Ventricular Tachycardia using Induced Pluripotent Stem Cell-derived CardiomyocytesAtara Novak0Avraham Lorber1Joseph Itskovitz-Eldor2Ofer Binah3The Sohnis Family Stem Cells Center, Technion - Israel Institute of Technology, Haifa, Israel; The Rappaport Family Institute for Research in the Medical Sciences, Technion - Israel Institute of Technology, Haifa, Israel; Ruth & Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, IsraelRuth & Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel; Department of Pediatric Cardiology, Rambam Health Care Campus, Haifa, Israel;The Sohnis Family Stem Cells Center, Technion - Israel Institute of Technology, Haifa, Israel; Ruth & Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel; Department of Obstetrics and Gynecology, Rambam Health Care Campus, Haifa, IsraelThe Sohnis Family Stem Cells Center, Technion - Israel Institute of Technology, Haifa, Israel; The Rappaport Family Institute for Research in the Medical Sciences, Technion - Israel Institute of Technology, Haifa, Israel; Ruth & Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, IsraelCatecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmogenic cardiac disorder characterized by life-threatening arrhythmias induced by physical or emotional stress, in the absence structural heart abnormalities. The arrhythmias may cause syncope or degenerate into cardiac arrest and sudden death which usually occurs during childhood. Recent studies have shown that CPVT is caused by mutations in the cardiac ryanodine receptor type 2 (RyR2) or calsequestrin 2 (CASQ2) genes. Both proteins are key contributors to the intracellular Ca2+ handling process and play a pivotal role in Ca2+ release from the sarcoplasmic reticulum to the cytosol during systole. Although the molecular pathogenesis of CPVT is not entirely clear, it was suggested that the CPVT mutations promote excessive sarcoplasmic reticulum Ca2+ leak, which initiates delayed afterdepolarizations (DADs) and triggered arrhythmias in cardiac myocytes. The recent breakthrough discovery of induced pluripotent stem cells (iPSC) generated from somatic cells (e.g. fibroblasts, keratinocytes) now enables researches to investigate mutated cardiomyocytes generated from the patient’s iPSC. To this end, in the present article we review recent studies on CPVT iPSC-derived cardiomyocytes, thus demonstrating in the mutated cells catecholamine-induced DADs and triggered arrhythmias.http://rmmj.org.il/Pages/ArticleHTM.aspx?manuId=224Adrenergic stimulationcardiac myocytescatecholaminergic polymorphic ventricular tachycardia (CPVT)delayed afterdepolarizationsinduced pluripotent stem cells (iPSC)inherited arrhythmias |
| spellingShingle | Atara Novak Avraham Lorber Joseph Itskovitz-Eldor Ofer Binah Modeling Catecholaminergic Polymorphic Ventricular Tachycardia using Induced Pluripotent Stem Cell-derived Cardiomyocytes Rambam Maimonides Medical Journal Adrenergic stimulation cardiac myocytes catecholaminergic polymorphic ventricular tachycardia (CPVT) delayed afterdepolarizations induced pluripotent stem cells (iPSC) inherited arrhythmias |
| title | Modeling Catecholaminergic Polymorphic Ventricular Tachycardia using Induced Pluripotent Stem Cell-derived Cardiomyocytes |
| title_full | Modeling Catecholaminergic Polymorphic Ventricular Tachycardia using Induced Pluripotent Stem Cell-derived Cardiomyocytes |
| title_fullStr | Modeling Catecholaminergic Polymorphic Ventricular Tachycardia using Induced Pluripotent Stem Cell-derived Cardiomyocytes |
| title_full_unstemmed | Modeling Catecholaminergic Polymorphic Ventricular Tachycardia using Induced Pluripotent Stem Cell-derived Cardiomyocytes |
| title_short | Modeling Catecholaminergic Polymorphic Ventricular Tachycardia using Induced Pluripotent Stem Cell-derived Cardiomyocytes |
| title_sort | modeling catecholaminergic polymorphic ventricular tachycardia using induced pluripotent stem cell derived cardiomyocytes |
| topic | Adrenergic stimulation cardiac myocytes catecholaminergic polymorphic ventricular tachycardia (CPVT) delayed afterdepolarizations induced pluripotent stem cells (iPSC) inherited arrhythmias |
| url | http://rmmj.org.il/Pages/ArticleHTM.aspx?manuId=224 |
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