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Updated: Dec 28, 2025
Generation and Expansion of Human Cardiomyocytes from Patient Peripheral Blood Mononuclear Cells
Published on: February 12, 2021
Aberrant expression of miR-29b-3p influences heart development and cardiomyocyte proliferation by targeting NOTCH2
Qian Yang1,2, Fang Wu1,2, Yaping Mi2
1Translational Medical Center for Development and Disease, Institute of Pediatrics, Shanghai Key Laboratory of Birth Defect, Children's Hospital of Fudan University, Shanghai, China.
Objectives:
microRNA-29 (miR-29) family have shown different expression patterns in cardiovascular diseases. Our study aims to explore the effect and mechanism of miR-29 family on cardiac development.
Materials And Methods:
A total of 13 patients with congenital heart disease (CHD) and 7 controls were included in our study. Tissues were obtained from the right ventricular outflow tract (RVOT) after surgical resection or autopsy. The next-generation sequencing was applied to screen the microRNA expression profiles of CHD. Quantitative RT-PCR and Western blot were employed to measure genes expression. Tg Cmlc2: GFP reporter zebrafish embryos were injected with microRNA (miRNA) to explore its role in cardiac development in vivo. Dual-luciferase reporter assay was designed to validate the target gene of miRNAs. CCK-8 and EdU incorporation assays were performed to evaluate cardiomyocyte proliferation.
Results:
Our study showed miR-29b-3p expression was significantly increased in the RVOT of the CHD patients. Injection of miR-29b-3p into zebrafish embryos induced higher mortality and malformation rates, developmental delay, cardiac malformation and dysfunction. miR-29b-3p inhibited cardiomyocyte proliferation, and its inhibitor promoted cardiomyocyte proliferation in vitro and in vivo. Furthermore, we identified that miR-29b-3p influenced cardiomyocyte proliferation by targeting NOTCH2, which was down-regulated in the RVOT of the CHD patients.
Conclusion:
This study reveals that miR-29b-3p functions as a novel regulator of cardiac development and inhibits cardiomyocyte proliferation via NOTCH2, which provides novel insights into the aetiology and potential treatment of CHD.
Insights
MicroRNA-29b-3p is elevated in congenital heart disease (CHD), inhibiting cardiac development by targeting NOTCH2. This finding offers new insights into CHD etiology and potential treatments.
Area of Science:
- Cardiovascular Biology
- Molecular Genetics
- Developmental Biology
Background:
- The microRNA-29 (miR-29) family exhibits varied expression in cardiovascular diseases.
- Understanding the role of specific miR-29 family members in cardiac development is crucial.
Purpose of the Study:
- To investigate the impact and mechanism of the miR-29 family on cardiac development.
- To explore the role of miR-29b-3p in congenital heart disease (CHD).
Main Methods:
- Next-generation sequencing and quantitative RT-PCR to profile microRNA expression in CHD tissues.
- Zebrafish model and in vitro assays (CCK-8, EdU) to assess miR-29b-3p effects on cardiac development and cardiomyocyte proliferation.
- Dual-luciferase reporter assay to identify NOTCH2 as a direct target of miR-29b-3p.
Main Results:
- miR-29b-3p expression was significantly upregulated in the right ventricular outflow tract (RVOT) of CHD patients.
- Overexpression of miR-29b-3p in zebrafish led to cardiac malformations, developmental delays, and increased mortality.
- miR-29b-3p inhibited cardiomyocyte proliferation, while its inhibitor promoted it, mediated through the downregulation of NOTCH2.
Conclusions:
- miR-29b-3p acts as a novel regulator of cardiac development, inhibiting cardiomyocyte proliferation.
- The miR-29b-3p/NOTCH2 axis provides new insights into the pathogenesis of CHD.
- This study suggests potential therapeutic targets for CHD based on miR-29b-3p and NOTCH2.
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