دورية أكاديمية
Modeling Reentry in the Short QT Syndrome With Human-Induced Pluripotent Stem Cell-Derived Cardiac Cell Sheets.
| العنوان: | Modeling Reentry in the Short QT Syndrome With Human-Induced Pluripotent Stem Cell-Derived Cardiac Cell Sheets. |
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| المؤلفون: | Shinnawi R; Sohnis Research Laboratory for Cardiac Electrophysiology and Regenerative Medicine, Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa, Israel., Shaheen N; Sohnis Research Laboratory for Cardiac Electrophysiology and Regenerative Medicine, Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa, Israel., Huber I; Sohnis Research Laboratory for Cardiac Electrophysiology and Regenerative Medicine, Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa, Israel., Shiti A; Sohnis Research Laboratory for Cardiac Electrophysiology and Regenerative Medicine, Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa, Israel., Arbel G; Sohnis Research Laboratory for Cardiac Electrophysiology and Regenerative Medicine, Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa, Israel., Gepstein A; Sohnis Research Laboratory for Cardiac Electrophysiology and Regenerative Medicine, Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa, Israel., Ballan N; Sohnis Research Laboratory for Cardiac Electrophysiology and Regenerative Medicine, Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa, Israel., Setter N; Sohnis Research Laboratory for Cardiac Electrophysiology and Regenerative Medicine, Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa, Israel., Tijsen AJ; Sohnis Research Laboratory for Cardiac Electrophysiology and Regenerative Medicine, Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa, Israel., Borggrefe M; First Department of Medicine, Faculty of Medicine, University Medical Centre Mannheim, University of Heidelberg, Mannheim, Germany; DZHK (German Center for Cardiovascular Research), Partner Site, Heidelberg-Mannheim, Mannheim, Germany., Gepstein L; Sohnis Research Laboratory for Cardiac Electrophysiology and Regenerative Medicine, Rappaport Faculty of Medicine and Research Institute, Technion-Israel Institute of Technology, Haifa, Israel; Cardiolology Department of Rambam Medical Center, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel. Electronic address: mdlior@technion.ac.il. |
| المصدر: | Journal of the American College of Cardiology [J Am Coll Cardiol] 2019 May 14; Vol. 73 (18), pp. 2310-2324. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Biomedical Country of Publication: United States NLM ID: 8301365 Publication Model: Print Cited Medium: Internet ISSN: 1558-3597 (Electronic) Linking ISSN: 07351097 NLM ISO Abbreviation: J Am Coll Cardiol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [New York, N.Y.] : Elsevier Biomedical, [c1983- |
| مواضيع طبية MeSH: | Arrhythmias, Cardiac*/diagnosis , Arrhythmias, Cardiac*/genetics , Arrhythmias, Cardiac*/metabolism , Arrhythmias, Cardiac*/prevention & control, Myocytes, Cardiac/*metabolism, Action Potentials ; Anti-Arrhythmia Agents/pharmacology ; Cells, Cultured ; ERG1 Potassium Channel/genetics ; Humans ; Induced Pluripotent Stem Cells ; Mutation ; Patch-Clamp Techniques ; Patient-Specific Modeling |
| مستخلص: | Background: The short QT syndrome (SQTS) is an inherited arrhythmogenic syndrome characterized by abnormal ion channel function, life-threatening arrhythmias, and sudden cardiac death. Objectives: The purpose of this study was to establish a patient-specific human-induced pluripotent stem cell (hiPSC) model of the SQTS, and to provide mechanistic insights into its pathophysiology and therapy. Methods: Patient-specific hiPSCs were generated from a symptomatic SQTS patient carrying the N588K mutation in the KCNH2 gene, differentiated into cardiomyocytes, and compared with healthy and isogenic (established by CRISPR/Cas9-based mutation correction) control hiPSC-derived cardiomyocytes (hiPSC-CMs). Patch-clamp was used to evaluate action-potential (AP) and I Results: Intracellular recordings demonstrated shortened action-potential duration (APD) and abbreviated refractory period in the SQTS-hiPSC-CMs. Similarly, voltage- and AP-clamp recordings revealed increased I Conclusions: A novel hiPSC-based model of the SQTS was established at both the cellular and tissue levels. This model recapitulated the disease phenotype in the culture dish and provided important mechanistic insights into arrhythmia mechanisms in the SQTS and its treatment. (Copyright © 2019. Published by Elsevier Inc.) |
| التعليقات: | Comment in: J Am Coll Cardiol. 2019 May 14;73(18):2325-2327. (PMID: 31072577) |
| فهرسة مساهمة: | Keywords: disease modeling; gene editing; induced pluripotent stem cells; optical mapping; reentry; short QT syndrome |
| المشرفين على المادة: | 0 (Anti-Arrhythmia Agents) 0 (ERG1 Potassium Channel) 0 (KCNH2 protein, human) |
| SCR Disease Name: | Short Qt Syndrome |
| تواريخ الأحداث: | Date Created: 20190511 Date Completed: 20200302 Latest Revision: 20200302 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1016/j.jacc.2019.02.055 |
| PMID: | 31072576 |
| قاعدة البيانات: | MEDLINE |
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Full Text Finder | تدمد: | 1558-3597 |
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| DOI: | 10.1016/j.jacc.2019.02.055 |