Please use this identifier to cite or link to this item: https://doi.org/10.1016/j.ijcard.2013.08.015
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dc.titleModeling type 3 long QT syndrome with cardiomyocytes derived from patient-specific induced pluripotent stem cells
dc.contributor.authorMa, D.
dc.contributor.authorWei, H.
dc.contributor.authorZhao, Y.
dc.contributor.authorLu, J.
dc.contributor.authorLi, G.
dc.contributor.authorSahib, N.B.E.
dc.contributor.authorTan, T.H.
dc.contributor.authorWong, K.Y.
dc.contributor.authorShim, W.
dc.contributor.authorWong, P.
dc.contributor.authorCook, S.A.
dc.contributor.authorLiew, R.
dc.date.accessioned2016-06-01T10:29:47Z
dc.date.available2016-06-01T10:29:47Z
dc.date.issued2013-10-15
dc.identifier.citationMa, D., Wei, H., Zhao, Y., Lu, J., Li, G., Sahib, N.B.E., Tan, T.H., Wong, K.Y., Shim, W., Wong, P., Cook, S.A., Liew, R. (2013-10-15). Modeling type 3 long QT syndrome with cardiomyocytes derived from patient-specific induced pluripotent stem cells. International Journal of Cardiology 168 (6) : 5277-5286. ScholarBank@NUS Repository. https://doi.org/10.1016/j.ijcard.2013.08.015
dc.identifier.issn01675273
dc.identifier.urihttp://scholarbank.nus.edu.sg/handle/10635/124796
dc.description.abstractBackground Type 3 long QT syndrome (LQT3) is the third most common form of LQT syndrome and is characterized by QT-interval prolongation resulting from a gain-of-function mutation in SCN5A. We aimed to establish a patient-specific human induced pluripotent stem cell (hiPSC) model of LQT3, which could be used for future drug testing and development of novel treatments for this inherited disorder. Methods and results Dermal fibroblasts obtained from a patient with LQT3 harboring a SCN5A mutation (c.5287G > A; p.V1763M) were reprogrammed to hiPSCs via repeated transfection of mRNA encoding OCT-4, SOX-2, KLF-4, C-MYC and LIN-28. hiPSC-derived cardiomyocytes (hiPSC-CMs) were obtained via cardiac differentiation. hiPSC-CMs derived from the patient's healthy sister were used as a control. Compared to the control, patient hiPSC-CMs exhibited dominant mutant SCN5A allele gene expression, significantly prolonged action potential duration or APD (paced CMs of control vs. patient: 226.50 ± 17.89 ms vs. 536.59 ± 37.1 ms; mean ± SEM, p < 0.005), an increased tetrodotoxin (TTX)-sensitive late or persistent Na+ current (control vs. patient: 0.65 ± 0.11 vs. 3.16 ± 0.27 pA/pF; n = 9, p < 0.01), a positive shift of steady state inactivation and a faster recovery from inactivation. Mexiletine, a NaV1.5 blocker, reversed the elevated late Na + current and prolonged APD in LQT3 hiPSC-CMs. Conclusions We demonstrate that hiPSC-CMs derived from a LQT3 patient recapitulate the biophysical abnormalities that define LQT3. The clinical significance of such an in vitro model is in the development of novel therapeutic strategies and a more personalized approach in testing drugs on patients with LQT3. © 2013 Elsevier Ireland Ltd © 2013 Published by Elsevier Ireland Ltd.
dc.description.urihttp://libproxy1.nus.edu.sg/login?url=http://dx.doi.org/10.1016/j.ijcard.2013.08.015
dc.sourceScopus
dc.subjectCardiomyocytes
dc.subjectInduced pluripotent stem cells
dc.subjectLong QT syndrome
dc.subjectSCN5A
dc.subjectSodium channel
dc.typeArticle
dc.contributor.departmentDUKE-NUS GRADUATE MEDICAL SCHOOL S'PORE
dc.description.doi10.1016/j.ijcard.2013.08.015
dc.description.sourcetitleInternational Journal of Cardiology
dc.description.volume168
dc.description.issue6
dc.description.page5277-5286
dc.description.codenIJCDD
dc.identifier.isiut000326220300034
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