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Identifying Features of Cardiac Disease Phenotypes Based on Mechanical Function in a Catecholaminergic Polymorphic Ventricular Tachycardia Model
Catecholaminergic polymorphic ventricular tachycardia (CPVT) is characterized by an arrhythmogenic mechanism involving disruption of calcium handling. This genetic disease can lead to sudden death in children and young adults during physical or emotional stress. Prior CPVT studies have focused on ca...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9127198/ https://www.ncbi.nlm.nih.gov/pubmed/35620470 http://dx.doi.org/10.3389/fbioe.2022.873531 |
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author | Stempien, A. Josvai, M. de Lange, W. J. Hernandez, J. J. Notbohm, J. Kamp, T. J. Valdivia, H. H. Eckhardt, L. L. Maginot, K. R. Ralphe, J. C. Crone, W. C. |
author_facet | Stempien, A. Josvai, M. de Lange, W. J. Hernandez, J. J. Notbohm, J. Kamp, T. J. Valdivia, H. H. Eckhardt, L. L. Maginot, K. R. Ralphe, J. C. Crone, W. C. |
author_sort | Stempien, A. |
collection | PubMed |
description | Catecholaminergic polymorphic ventricular tachycardia (CPVT) is characterized by an arrhythmogenic mechanism involving disruption of calcium handling. This genetic disease can lead to sudden death in children and young adults during physical or emotional stress. Prior CPVT studies have focused on calcium handling, but mechanical functionality has rarely been investigated in vitro. In this research we combine stem cell-derived cardiomyocytes from a CPVT patient (RyR2-H2464D mutation) and a healthy familial control with an engineered culture platform to evaluate mechanical function of cardiomyocytes. Substrates with Young’s modulus ranging from 10 to 50 kPa were used in conjunction with microcontact printing of ECM proteins into defined patterns for subsequent attachment. Digital Image Correlation (DIC) was used to evaluate collections of contracting cells. The amplitude of contractile strain was utilized as a quantitative indicator of functionality and disease severity. We found statistically significant differences: the maximum contractile strain was consistently higher in patient samples compared to control samples on all substrate stiffnesses. Additionally, the patient cell line had a statistically significantly slower intrinsic contraction rate than the control, which agrees with prior literature. Differences in mechanical strain have not been previously reported, and hypercontractility is not a known characteristic of CPVT. However, functional changes can occur as the disease progresses, thus this observation may not represent behavior observed in adolescent and adult patients. These results add to the limited studies of mechanical function of CPVT CMs reported in literature and identify functional differences that should be further explored. |
format | Online Article Text |
id | pubmed-9127198 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-91271982022-05-25 Identifying Features of Cardiac Disease Phenotypes Based on Mechanical Function in a Catecholaminergic Polymorphic Ventricular Tachycardia Model Stempien, A. Josvai, M. de Lange, W. J. Hernandez, J. J. Notbohm, J. Kamp, T. J. Valdivia, H. H. Eckhardt, L. L. Maginot, K. R. Ralphe, J. C. Crone, W. C. Front Bioeng Biotechnol Bioengineering and Biotechnology Catecholaminergic polymorphic ventricular tachycardia (CPVT) is characterized by an arrhythmogenic mechanism involving disruption of calcium handling. This genetic disease can lead to sudden death in children and young adults during physical or emotional stress. Prior CPVT studies have focused on calcium handling, but mechanical functionality has rarely been investigated in vitro. In this research we combine stem cell-derived cardiomyocytes from a CPVT patient (RyR2-H2464D mutation) and a healthy familial control with an engineered culture platform to evaluate mechanical function of cardiomyocytes. Substrates with Young’s modulus ranging from 10 to 50 kPa were used in conjunction with microcontact printing of ECM proteins into defined patterns for subsequent attachment. Digital Image Correlation (DIC) was used to evaluate collections of contracting cells. The amplitude of contractile strain was utilized as a quantitative indicator of functionality and disease severity. We found statistically significant differences: the maximum contractile strain was consistently higher in patient samples compared to control samples on all substrate stiffnesses. Additionally, the patient cell line had a statistically significantly slower intrinsic contraction rate than the control, which agrees with prior literature. Differences in mechanical strain have not been previously reported, and hypercontractility is not a known characteristic of CPVT. However, functional changes can occur as the disease progresses, thus this observation may not represent behavior observed in adolescent and adult patients. These results add to the limited studies of mechanical function of CPVT CMs reported in literature and identify functional differences that should be further explored. Frontiers Media S.A. 2022-05-10 /pmc/articles/PMC9127198/ /pubmed/35620470 http://dx.doi.org/10.3389/fbioe.2022.873531 Text en Copyright © 2022 Stempien, Josvai, de Lange, Hernandez, Notbohm, Kamp, Valdivia, Eckhardt, Maginot, Ralphe and Crone. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Bioengineering and Biotechnology Stempien, A. Josvai, M. de Lange, W. J. Hernandez, J. J. Notbohm, J. Kamp, T. J. Valdivia, H. H. Eckhardt, L. L. Maginot, K. R. Ralphe, J. C. Crone, W. C. Identifying Features of Cardiac Disease Phenotypes Based on Mechanical Function in a Catecholaminergic Polymorphic Ventricular Tachycardia Model |
title | Identifying Features of Cardiac Disease Phenotypes Based on Mechanical Function in a Catecholaminergic Polymorphic Ventricular Tachycardia Model |
title_full | Identifying Features of Cardiac Disease Phenotypes Based on Mechanical Function in a Catecholaminergic Polymorphic Ventricular Tachycardia Model |
title_fullStr | Identifying Features of Cardiac Disease Phenotypes Based on Mechanical Function in a Catecholaminergic Polymorphic Ventricular Tachycardia Model |
title_full_unstemmed | Identifying Features of Cardiac Disease Phenotypes Based on Mechanical Function in a Catecholaminergic Polymorphic Ventricular Tachycardia Model |
title_short | Identifying Features of Cardiac Disease Phenotypes Based on Mechanical Function in a Catecholaminergic Polymorphic Ventricular Tachycardia Model |
title_sort | identifying features of cardiac disease phenotypes based on mechanical function in a catecholaminergic polymorphic ventricular tachycardia model |
topic | Bioengineering and Biotechnology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9127198/ https://www.ncbi.nlm.nih.gov/pubmed/35620470 http://dx.doi.org/10.3389/fbioe.2022.873531 |
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