Modeling Secondary Iron Overload Cardiomyopathy with Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.
Cell Rep
; 32(2): 107886, 2020 07 14.
Article
in En
| MEDLINE
| ID: mdl-32668256
ABSTRACT
Excessive iron accumulation in the heart causes iron overload cardiomyopathy (IOC), which initially presents as diastolic dysfunction and arrhythmia but progresses to systolic dysfunction and end-stage heart failure when left untreated. However, the mechanisms of iron-related cardiac injury and how iron accumulates in human cardiomyocytes are not well understood. Herein, using human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs), we model IOC and screen for drugs to rescue the iron overload phenotypes. Human iPSC-CMs under excess iron exposure recapitulate early-stage IOC, including oxidative stress, arrhythmia, and contractile dysfunction. We find that iron-induced changes in calcium kinetics play a critical role in dysregulation of CM functions. We identify that ebselen, a selective divalent metal transporter 1 (DMT1) inhibitor and antioxidant, could prevent the observed iron overload phenotypes, supporting the role of DMT1 in iron uptake into the human myocardium. These results suggest that ebselen may be a potential preventive and therapeutic agent for treating patients with secondary iron overload.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Iron Overload
/
Myocytes, Cardiac
/
Induced Pluripotent Stem Cells
/
Models, Biological
/
Cardiomyopathies
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Cell Rep
Year:
2020
Document type:
Article
Affiliation country:
United States