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Updated: May 8, 2026
Generation and Expansion of Human Cardiomyocytes from Patient Peripheral Blood Mononuclear Cells
Published on: February 12, 2021
Notch 1 signalling inhibits cardiomyocyte apoptosis in ischaemic postconditioning
1Department of Cardiovascular Surgery, The First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, China.
Insights
Notch 1 signalling protects heart cells from apoptosis after ischaemic postconditioning (IPost) by regulating Bcl-2, Bax, and caspase-9/-3. This pathway promotes cell survival and regeneration following heart injury.
Area of Science:
- Cardiovascular Biology
- Molecular Cardiology
- Cellular Regeneration
Background:
- The Notch signalling pathway is crucial for cardiac repair post-myocardial infarction.
- The precise mechanisms of Notch-mediated cardioprotection during ischaemic postconditioning (IPost) remain incompletely understood.
Purpose of the Study:
- To elucidate the mechanism by which Notch signalling mediates cardioprotection following IPost.
- To investigate the role of Notch 1 in regulating cardiomyocyte apoptosis and survival.
Main Methods:
- H9c2 cells were treated with hypoxia/reoxygenation (H/R) and subjected to IPost.
- Notch 1 expression was modulated using pcDNA3.1-Myc-His plasmid (activation) and RNA interference (inhibition).
- Cell apoptosis, proliferation, Bcl-2/Bax expression, and caspase-9/-3 activity were assessed.
Main Results:
- Notch 1 activation significantly reduced cardiomyocyte apoptosis and promoted cell proliferation.
- Upregulation of Bcl-2 and downregulation of Bax were observed with Notch 1 activation.
- Increased caspase-9/-3 activities were associated with Notch 1 signalling, indicating apoptosis regulation.
Conclusions:
- Notch 1 signalling confers cardioprotection by inhibiting cardiomyocyte apoptosis.
- Regulation of Bcl-2, Bax, and caspase-9/-3 activation are key mechanisms involved.
- Targeting Notch 1 may offer therapeutic strategies for post-ischaemic cardiac recovery.
Aim:
Recent studies have demonstrated that Notch signalling pathway is an important mediator of cardiac repair and regeneration after myocardial infarction. However, the mechanism by which Notch signalling pathway is mediating cardioprotection after ischaemic postconditioning (IPost) is still not understood thoroughly. The aim of the present study was to investigate the mechanism by which Notch signalling pathway mediated the cardioprotection effect after IPost.
Methods:
Rat heart-derived H9c2 cells were randomly divided into six groups as follows: Control group, hypoxia/reoxygenation group (H/R), H/R+N1ICD group, H-post group, H-post+Notch-1miRNA group, and Mock group. We used pcDNA3.1-Myc-His plasmid and RNA interference (RNAi) to activate/inhibit the expression of Notch-1 in H9c2 cell lines. The Bcl-2, Bax genes and proteins were assessed by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and Western blot analysis. The effects of Notch 1 signalling on cell survival, proliferation and apoptosis were detected by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) and flow cytometry analysis, respectively. Furthermore, Notch 1 signalling induced the disruption of mitochondrial membrane potential, thus leading to the activation of caspase-9/-3 measured using the colorimetric activity assay.
Results:
We found Notch 1 signalling reduced cardiomyocyte apoptosis in IPost through regulating the expression of Bcl-2, Bax and activation of caspase-9 and -3. We found that after transfected with pcDNA3.1-Myc-His plasmid, activation of the Notch 1 gene effectively promoted cell proliferation and inhibited apoptosis. The Notch 1 upregulation was accompanied by an upregulation of Bcl-2 and a downregulation of Bax. In addition, a paralled increase in caspase-9/-3 activities was observed. These effects were blunted by transfected with Notch-1 miRNA in the H9c2 cells.
Conclusion:
Notch 1 signalling has a cardioprotection effect, which may result from cardiomyocyte apoptosis, by means of regulating the expression of cell apoptosis inhibiting proteins Bcl-2, Bax and the activation of caspase-9 and -3.
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