- 著者
- Taku Sakai Atsuhiko T. Naito Yuki Kuramoto Masamichi Ito Katsuki Okada Tomoaki Higo Akito Nakagawa Masato Shibamoto Toshihiro Yamaguchi Tomokazu Sumida Seitaro Nomura Akihiro Umezawa Shigeru Miyagawa Yoshiki Sawa Hiroyuki Morita Jong-Kook Lee Ichiro Shiojima Yasushi Sakata Issei Komuro
- 出版者
- International Heart Journal Association
- 雑誌
- International Heart Journal (ISSN:13492365)
- 巻号頁・発行日
- pp.17-730, (Released:2018-08-11)
- 参考文献数
- 28
- 被引用文献数
- 13
Hypertrophic cardiomyopathy (HCM) is a genetic disorder that is characterized by hypertrophy of the myocardium. Some of the patients are diagnosed for HCM during infancy, and the prognosis of infantile HCM is worse than general HCM. Nevertheless, pathophysiology of infantile HCM is less investigated and remains largely unknown. In the present study, we generated induced pluripotent stem cells (iPSCs) from two patients with infantile HCM: one with Noonan syndrome and the other with idiopathic HCM. We found that iPSC-derived cardiomyocytes (iPSC-CMs) from idiopathic HCM patient were significantly larger and showed higher diastolic intracellular calcium concentration compared with the iPSC-CMs from healthy subject. Unlike iPSC-CMs from the adult/adolescent HCM patient, arrhythmia was not observed as a disease-related phenotype in iPSC-CMs from idiopathic infantile HCM patient. Phenotypic screening revealed that Pyr3, a transient receptor potential channel 3 channel inhibitor, decreased both the cell size and diastolic intracellular calcium concentration in iPSC-CMs from both Noonan syndrome and idiopathic infantile HCM patients, suggesting that the target of Pyr3 may play a role in the pathogenesis of infantile HCM, regardless of the etiology. Further research may unveil the possibility of Pyr3 or its derivatives in the treatment of infantile HCM.