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Murine Myocardial Infarction Model using Permanent Ligation of Left Anterior Descending Coronary Artery
Published on: August 16, 2019
Nogo-C regulates cardiomyocyte apoptosis during mouse myocardial infarction
Shi Jia1, Xue Qiao1, Jingjing Ye1
1Department of Physiology and Pathophysiology, Health Science Center, Peking University, Beijing 100191, China.
Abstract:
Myocardial infarction is caused by insufficient coronary blood supply, which leads to myocardial damage and eventually the heart failure. Molecular mechanisms associated with the loss of cardiomyocytes during myocardial infarction (MI) and ischemia-related cardiac diseases are not yet fully understood. Nogo-C is an endoplasmic reticulum protein ubiquitously expressed in tissues including in the heart, however, the cardiac function of Nogo-C is still unknown. In the present study, we found that Nogo-C was upregulated in mouse hearts after MI, and hypoxic treatments also increased Nogo-C protein level in cardiomyocytes. Adenovirus mediated overexpression of Nogo-C led to cardiomyocyte apoptosis, whereas knockdown of Nogo-c by shRNA protected cardiomyocytes from hypoxia-induced cell apoptosis. Importantly, Nogo-C knockout mice displayed improved cardiac function, smaller infarct area, and less apoptotic cells after MI. Moreover, we found that miR-182 negatively regulated Nogo-C expression and was downregulated during MI, expressing miR-182 in cardiomyocytes protected hypoxia- and Nogo-C-mediated cell apoptosis. Our results indicate that increased cardiac Nogo-C expression is both sufficient and necessary for ischemia-induced cardiomyocyte apoptosis and cardiac dysfunction, suggesting that deregulation of Nogo-C by miRNA may be a potential therapeutic target for ischemia-related heart diseases.
Insights
Myocardial infarction (MI) leads to heart failure. This study reveals Nogo-C protein promotes heart cell death after MI and suggests targeting Nogo-C with microRNAs could treat heart disease.
Area of Science:
- Cardiology
- Molecular Biology
- Cell Biology
Background:
- Myocardial infarction (MI) causes heart failure due to cardiomyocyte loss, but underlying molecular mechanisms remain unclear.
- Nogo-C, an endoplasmic reticulum protein, is present in the heart, yet its cardiac role is unknown.
- Understanding cardiomyocyte loss in ischemia-related heart diseases is crucial for developing effective therapies.
Purpose of the Study:
- To investigate the role of Nogo-C in myocardial infarction and ischemia-induced cardiomyocyte apoptosis.
- To explore the regulatory relationship between Nogo-C and microRNA-182 (miR-182) in cardiac function.
- To assess the therapeutic potential of targeting Nogo-C and miR-182 in heart disease.
Main Methods:
- Utilized mouse models of myocardial infarction and hypoxic conditions.
- Employed adenovirus-mediated overexpression and shRNA-mediated knockdown of Nogo-C in cardiomyocytes.
- Analyzed Nogo-C expression, cardiomyocyte apoptosis, cardiac function, and miR-182 levels.
Main Results:
- Nogo-C expression was upregulated in mouse hearts post-MI and by hypoxia in cardiomyocytes.
- Nogo-C overexpression induced cardiomyocyte apoptosis, while Nogo-C knockdown protected against hypoxia-induced apoptosis.
- Nogo-C knockout mice showed improved cardiac function and reduced infarct size after MI.
- miR-182 negatively regulated Nogo-C and its expression was decreased during MI; miR-182 delivery protected against apoptosis.
Conclusions:
- Increased cardiac Nogo-C is essential for ischemia-induced cardiomyocyte apoptosis and cardiac dysfunction.
- Deregulation of Nogo-C by miR-182 plays a significant role in the pathogenesis of MI.
- Targeting Nogo-C or modulating miR-182 offers a potential therapeutic strategy for ischemia-related heart diseases.
