Circular RNA Expression for Dilated Cardiomyopathy in Hearts and Pluripotent Stem Cell-Derived Cardiomyocytes
Yiyu Zhang1, Guoqing Huang1, Zhaohu Yuan2
1Department of Blood Transfusion, Department of Cardiology, Shenzhen Longhua District Central Hospital, The Affiliated Central Hospital of Shenzhen Longhua District, Guangdong Medical University, Shenzhen, China.
Insights
Dilated cardiomyopathy (DCM) is a heart condition where ventricles enlarge, impacting contractility. This review explores circular RNAs and stem cell models in understanding DCM development and potential treatments.
Area of Science:
- Cardiovascular Biology
- Molecular Genetics
- Stem Cell Biology
Background:
- Dilated cardiomyopathy (DCM) is characterized by ventricular enlargement and impaired contractility, often leading to heart failure.
- Circular RNAs (circRNAs) are noncoding RNAs with cell-type specificity, increasingly recognized for their role in heart failure and DCM.
- Human-induced pluripotent stem cell (hiPSC) technology enables modeling of genetic mutations causing cardiac disorders.
Purpose of the Study:
- To review the expression and mechanisms of circRNAs in DCM.
- To update on scientific progress in modeling gene mutation-induced DCM using hiPSCs.
- To enhance understanding of DCM development and pathophysiology at the molecular level.
Main Methods:
- Review of current literature on circRNAs in DCM.
- Analysis of hiPSC technology for modeling genetic DCM.
- Examination of genome editing applications in DCM research.
Main Results:
- CircRNAs play a regulatory role in heart failure and DCM.
- hiPSC models provide cellular-level insights into DCM.
- Genome editing can correct gene defects and rescue disease phenotypes in patient-derived iPSCs.
Conclusions:
- Understanding circRNA expression and mechanisms is crucial for DCM pathophysiology.
- hiPSC-based modeling and genome editing offer promising avenues for DCM research and therapeutic development.
Abstract:
Dilated cardiomyopathy (DCM) is a type of heart disease delimited by enlargement and dilation of one or both of the ventricles along with damaged contractility, which is often accompanied by the left ventricular ejection fraction (LVEF) less than 40%. DCM is progressive and always leads to heart failure. Circular RNAs (circRNAs) are unique species of noncoding RNAs featuring high cell-type specificity and long-lasting conservation, which normally are involved in the regulation of heart failure and DCM recently. So far, a landscape of various single gene or polygene mutations, which can cause complex human cardiac disorders, has been investigated by human-induced pluripotent stem cell (hiPSC) technology. Furthermore, DCM has been modeled as well, providing new perspectives on the disease study at a cellular level. In addition, current genome editing methods can not only repair defects of some genes, but also rescue the disease phenotype in patient-derived iPSCs, even introduce pathological-related mutations into wild-type strains. In this review, we gather up the aspects of the circRNA expression and mechanism in the DCM disease scenario, facilitating understanding in DCM development and pathophysiology in the molecular level. Also, we offer an update on the most relevant scientific progress in iPSC modeling of gene mutation-induced DCM.


