Inhibition of the NOTCH1 Pathway in the Stressed Heart Limits Fibrosis and Promotes Recruitment of Non-Myocyte Cells into the Cardiomyocyte Fate
Abstract
:1. Introduction
2. Materials and Methods
2.1. Animals
2.2. Lineage Tracing
2.3. Surgery and Echocardiography
2.4. Antibody, BrdU and GapmeR Administration
2.5. RNA Isolation and Quantitative RT-PCR Analysis
2.6. Immunofluorescence Staining
2.7. Isolation of CMs and Non-Myocyte Cells from Adult Mouse Hearts
2.8. Histology and Fibrosis Measurements
2.9. Transfection of P19Cl6 Cells and Activation of Wisper Expression
2.10. Statistical Analysis
3. Results
3.1. The NOTCH Signaling Pathway Is Activated in Cardiac Non-Myocyte Cells Isolated from the Stressed Heart
3.2. NOTCH1 Blockade Inhibits Pressure Overload-Induced Hypertrophy and Preserves Cardiac Function
3.3. NOTCH1 Blockade Reduces Cardiac Fibrosis in the Stressed Heart
3.4. NOTCH1-Activated Cells Contribute to Non-Myocyte Cell Formation
3.5. NOTCH Blockade Stimulates CM Formation from Non-Myocyte Cells in the Stressed Heart
3.6. NOTCH-Independent Reduction in Cardiac Fibrosis Favors New CM Formation
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Nemir, M.; Kay, M.; Maison, D.; Berthonneche, C.; Sarre, A.; Plaisance, I.; Pedrazzini, T. Inhibition of the NOTCH1 Pathway in the Stressed Heart Limits Fibrosis and Promotes Recruitment of Non-Myocyte Cells into the Cardiomyocyte Fate. J. Cardiovasc. Dev. Dis. 2022, 9, 111. https://doi.org/10.3390/jcdd9040111
Nemir M, Kay M, Maison D, Berthonneche C, Sarre A, Plaisance I, Pedrazzini T. Inhibition of the NOTCH1 Pathway in the Stressed Heart Limits Fibrosis and Promotes Recruitment of Non-Myocyte Cells into the Cardiomyocyte Fate. Journal of Cardiovascular Development and Disease. 2022; 9(4):111. https://doi.org/10.3390/jcdd9040111
Chicago/Turabian StyleNemir, Mohamed, Maryam Kay, Damien Maison, Corinne Berthonneche, Alexandre Sarre, Isabelle Plaisance, and Thierry Pedrazzini. 2022. "Inhibition of the NOTCH1 Pathway in the Stressed Heart Limits Fibrosis and Promotes Recruitment of Non-Myocyte Cells into the Cardiomyocyte Fate" Journal of Cardiovascular Development and Disease 9, no. 4: 111. https://doi.org/10.3390/jcdd9040111