Novel Calmodulin Variant p.E46K Associated With Severe Catecholaminergic Polymorphic Ventricular Tachycardia Produces Robust Arrhythmogenicity in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.

Jingshan Gao Takeru Makiyama Yuta Yamamoto Takuya KobayashiHisaaki AokiThomas L MaurissenYimin WuriyanghaiAsami Kashiwa Tomohiko Imamura Takanori Aizawa Hai Huang Hirohiko KohjitaniMisato NishikawaKazuhisa Chonabayashi Megumi FukuyamaHiromi ManabeKouichi NakauTsutomu WadaKoichi Kato Futoshi Toyoda Yoshinori Yoshida Naomasa Makita Knut Woltjen Seiko Ohno Nagomi Kurebayashi Takashi MurayamaTakashi SakuraiMinoru Horie Takeshi Kimura

Published in: Circulation. Arrhythmia and electrophysiology (2023)

We, for the first time, established a CaM-related CPVT iPSC-CM model which recapitulated severe arrhythmogenic features resulting from E46K-CaM dominantly binding and facilitating RyR2. In addition, the findings in iPSC-based drug testing will contribute to precision medicine.

Keyphrases

induced pluripotent stem cells
drug induced
high glucose
endothelial cells
early onset
diabetic rats
oxidative stress
pluripotent stem cells
dna binding
binding protein
transcription factor