| RRC ID |
82507
|
| Author |
Mori H, Xu D, Shimoda Y, Yuan Z, Murakata Y, Xi B, Sato K, Yamamoto M, Tajiri K, Ishizu T, Ieda M, Murakoshi N.
|
| Title |
Metabolic remodeling and calcium handling abnormality in induced pluripotent stem cell-derived cardiomyocytes in dilated phase of hypertrophic cardiomyopathy with MYBPC3 frameshift mutation.
|
| Journal |
Sci Rep
|
| Abstract |
Hypertrophic cardiomyopathy (HCM) is an inherited disorder characterized by left ventricular hypertrophy and diastolic dysfunction, and increases the risk of arrhythmias and heart failure. Some patients with HCM develop a dilated phase of hypertrophic cardiomyopathy (D-HCM) and have poor prognosis; however, its pathogenesis is unclear and few pathological models exist. This study established disease-specific human induced pluripotent stem cells (iPSCs) from a patient with D-HCM harboring a mutation in MYBPC3 (c.1377delC), a common causative gene of HCM, and investigated the associated pathophysiological mechanisms using disease-specific iPSC-derived cardiomyocytes (iPSC-CMs). We confirmed the expression of pluripotent markers and the ability to differentiate into three germ layers in D-HCM patient-derived iPSCs (D-HCM iPSCs). D-HCM iPSC-CMs exhibited disrupted myocardial sarcomere structures and an increased number of damaged mitochondria. Ca2+ imaging showed increased abnormal Ca2+ signaling and prolonged decay time in D-HCM iPSC-CMs. Cell metabolic analysis revealed increased basal respiration, maximal respiration, and spare-respiratory capacity in D-HCM iPSC-CMs. RNA sequencing also showed an increased expression of mitochondrial electron transport system-related genes. D-HCM iPSC-CMs showed abnormal Ca2+ handling and hypermetabolic state, similar to that previously reported for HCM patient-derived iPSC-CMs. Although further studies are required, this is expected to be a useful pathological model for D-HCM.
|
| Volume |
14(1)
|
| Pages |
15422
|
| Published |
2024-7-4
|
| DOI |
10.1038/s41598-024-62530-0
|
| PII |
10.1038/s41598-024-62530-0
|
| PMID |
38965264
|
| PMC |
PMC11224225
|
| MeSH |
Calcium* / metabolism
Calcium Signaling
Cardiomyopathy, Hypertrophic* / genetics
Cardiomyopathy, Hypertrophic* / metabolism
Cardiomyopathy, Hypertrophic* / pathology
Carrier Proteins* / genetics
Carrier Proteins* / metabolism
Cell Differentiation
Frameshift Mutation*
Humans
Induced Pluripotent Stem Cells* / metabolism
Male
Myocytes, Cardiac* / metabolism
Myocytes, Cardiac* / pathology
|
| Resource |
| Human and Animal Cells |
HPS3354
HPS3386 |
