Key result
Treatment of human-induced pluripotent stem cell-derived cardiomyocytes with arrhythmogenic drugs upregulated 19 genes, enabling the prediction of arrhythmogenic risk by scoring gene expression levels.
Why the study?
Does gene expression analysis in human-induced pluripotent stem cell-derived cardiomyocytes predict the arrhythmogenic potential of drugs?
Does gene expression analysis in human-induced pluripotent stem cell-derived cardiomyocytes predict the arrhythmogenic potential of drugs?
Answers are grounded in this paper and cite their sources.
A novel evaluation system using gene expression analysis in hiPS-CMs can accurately predict the arrhythmogenic potential of drugs associated with QT prolongation.
In recent years, human-induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) have been widely used to develop evaluation systems for drug cardiotoxicity, including the arrhythmia caused by QT prolongation. To accurately assess the arrhythmogenic potential of drugs, associated with QT prolongation, we developed an evaluation system using hiPS-CMs and gene expression analysis. hiPS-CMs were treated with 8 arrhythmogenic and 17 non-arrhythmogenic drugs at several concentrations for 24 hr to comprehensively analyze gene expression. The results showed that 19 genes were upregulated in the arrhythmogenic drug-treated cells compared with their expression levels in the non-treated and non-arrhythmogenic drug-treated cells. The arrhythmogenic risks of the drugs were evaluated by scoring gene expression levels. The results indicated that arrhythmogenic risks could be inferred when cells were treated at a concentration 100 times higher than the maximum blood concentration of the drug. Thus, we succeeded in developing a system for evaluation of the arrhythmogenic potential of drugs using gene expression analysis.
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Higa et al. (2017) conducted a letter in Arrhythmia and QT prolongation. Arrhythmogenic drugs vs. Non-arrhythmogenic drugs and vehicle control was evaluated on Upregulation of 19 specific genes (p=<1.0E-12). Treatment of human-induced pluripotent stem cell-derived cardiomyocytes with arrhythmogenic drugs upregulated 19 genes, enabling the prediction of arrhythmogenic risk by scoring gene expression levels.
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