Novel insights in the pathomechanism of Brugada syndrome and fever-related type 1 ECG changes in a preclinical study using human-induced pluripotent stem cell-derived cardiomyocytes
Summary
The study demonstrated that the SCN5A variant (c.3148G>A/p.Ala1050Thr) caused loss-of-function of sodium channels and increased the channel sensitivity to high temperature and LPS challenge in hiPSC-CMs from a BrS cell line with this variant but not in two non-BrS hiPSC-CM lines. The results suggest that LPS may exacerbate BrS phenotype via enhancing autophagy, whereas fever may exacerbate BrS phenotype via inhibiting PKA-signalling in BrS cardiomyocytes with but probably not limited to this variant. © 2022 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.
| Authors | Li Y, Dinkel H, Pakalniskyte D, Busley AV, Cyganek L, Zhong R, Zhang F, Xu Q, Maywald L, Aweimer A, Huang M, Liao Z, Meng Z, Yan C, Prädel T, Rose L, Moscu-Gregor A, Hohn A, Yang Z, Qiao L, Mügge A, Zhou X, Akin I, El-Battrawy I |
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| Journal | Clinical and translational medicine |
| Publication Date | 2023 Mar;13(3):e1130 |
| PubMed | 36881552 |
| PubMed Central | PMC9990896 |
| DOI | 10.1002/ctm2.1130 |