RRC ID 61922
著者 Sakai T, Naito AT, Kuramoto Y, Ito M, Okada K, Higo T, Nakagawa A, Shibamoto M, Yamaguchi T, Sumida T, Nomura S, Umezawa A, Miyagawa S, Sawa Y, Morita H, Lee JK, Shiojima I, Sakata Y, Komuro I.
タイトル Phenotypic Screening Using Patient-Derived Induced Pluripotent Stem Cells Identified Pyr3 as a Candidate Compound for the Treatment of Infantile Hypertrophic Cardiomyopathy.
ジャーナル Int Heart J
Abstract 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.
巻・号 59(5)
ページ 1096-1105
公開日 2018-9-26
DOI 10.1536/ihj.17-730
PMID 30101858
MeSH Adult Calcium / metabolism Cardiomyopathy, Hypertrophic / diagnosis Cardiomyopathy, Hypertrophic / drug therapy Cardiomyopathy, Hypertrophic / metabolism* Cardiomyopathy, Hypertrophic / pathology Child, Preschool Humans Induced Pluripotent Stem Cells / metabolism* Male Mass Screening / methods* Mutation Myocardium / pathology Myocytes, Cardiac / pathology Noonan Syndrome / diagnosis Noonan Syndrome / drug therapy Noonan Syndrome / metabolism* Noonan Syndrome / pathology Phenotype Prevalence Transient Receptor Potential Channels / antagonists & inhibitors* Transient Receptor Potential Channels / therapeutic use
IF 1.906
リソース情報
ヒト・動物細胞 253G1(HPS0002)