Blockade of RBP-J-Mediated Notch Signaling Pathway Exacerbates Cardiac Remodeling after Infarction by Increasing Apoptosis in Mice

Yanru He, Si Pang, Jia Huang, Kongbo Zhu, Jiayi Tong, Yao Liang Tang, Genshan Ma, Lijuan Chen

Research output: Contribution to journalArticle

Abstract

Background. Ischemic heart disease (IHD) is the major cause of death in patients with cardiovascular disease. Cardiac remodeling is a common pathological change following myocardial infarction (MI), and cardiomyocyte apoptosis plays a key role in this change. Transcription factor recombination signal-binding protein-J (RBP-J)-mediated Notch signaling pathway has been implicated in several inherited cardiovascular diseases, including aortic valve diseases, but whether the RBP-J-mediated Notch signaling pathway plays a role in cardiomyocyte apoptosis after MI is unclear. Method. We crossed RBP-Jfl/fl mice and Myh6-Cre/Esr1 transgenic mice to delete RBP-J in vivo and to partly inhibit the canonical Notch signaling pathway. MI was induced in mice by permanent ligation of the left anterior descending coronary artery followed by the knockout of RBP-J. Cardiac function and morphology were assessed by echocardiography and histological analysis 4 weeks after infarction. In addition, the expression and regulation of apoptosis-related molecules were examined by real time PCR and western blot. Results. RBP-J knockout decreased the survival rate and deteriorated post-MI remodeling and function in mice, and this effect was associated with increased cardiomyocyte apoptosis. The potential mechanisms might be related to the downregulated expression of bcl-2, upregulated expression of bax, and cleaved-caspase 3 to exacerbate cardiomyocyte apoptosis. Conclusion. These findings show that the RBP-J-mediated Notch signaling pathway in cardiomyocytes limits ventricular remodeling and improves cardiac function after MI. The RBP-J-mediated Notch signaling pathway has a protective role in cardiomyocyte apoptosis following cardiac injury.

Original languageEnglish (US)
Article number5207031
JournalBioMed Research International
Volume2018
DOIs
StatePublished - Jan 1 2018

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Immunoglobulin J Recombination Signal Sequence-Binding Protein
Cardiac Myocytes
Infarction
Carrier Proteins
Apoptosis
Myocardial Infarction
Cardiovascular Diseases
Echocardiography
Aortic Diseases
Ventricular Remodeling
Aortic Valve
Caspase 3
Transgenic Mice
Myocardial Ischemia
Ligation
Real-Time Polymerase Chain Reaction
Cause of Death
Coronary Vessels
Transcription Factors
Down-Regulation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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Blockade of RBP-J-Mediated Notch Signaling Pathway Exacerbates Cardiac Remodeling after Infarction by Increasing Apoptosis in Mice. / He, Yanru; Pang, Si; Huang, Jia; Zhu, Kongbo; Tong, Jiayi; Tang, Yao Liang; Ma, Genshan; Chen, Lijuan.

In: BioMed Research International, Vol. 2018, 5207031, 01.01.2018.

Research output: Contribution to journalArticle

He, Yanru ; Pang, Si ; Huang, Jia ; Zhu, Kongbo ; Tong, Jiayi ; Tang, Yao Liang ; Ma, Genshan ; Chen, Lijuan. / Blockade of RBP-J-Mediated Notch Signaling Pathway Exacerbates Cardiac Remodeling after Infarction by Increasing Apoptosis in Mice. In: BioMed Research International. 2018 ; Vol. 2018.
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