PLAC8 as a potential therapeutic target for myocardial infarction: unraveling the molecular mechanisms
Yifan Tong1, Xin Huang2, Wei Qian3
1Department of Cardiology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, 17 Yongwai Zhengjie, Nanchang, Jiangxi Province, 330006, China. ndyfy09574@ncu.edu.cn.
Abstract:
The incidence of myocardial infarction (MI) has been increasing in recent years, and the cause of acute myocardial infarction is apoptosis due to insufficient coronary myocardial blood supply. PLAC8 is a critical gene in the disease process of MI through GEO database research and analysis of differentially expressed genes (DEGs). In this study, in mice with myocardial infarction caused by surgical ligation of the left anterior descending coronary artery (LAD) and hypoxia-induced H9C2 cells as a model, the myocardium of the model group was found to show severe cardiomyocyte disorders, apoptosis of inflammatory cell infiltration, and ischemic state by HE, TTC, and Tunel staining. The expression of PLAC8 was reduced in the disease model by PCR and Western blot, and the expression of cle-Casp3 and Bax was also found to be high. However, overexpression of PLAC8 in the disease model reversed these processes. MEK/ERK and P65 are the core signaling pathways in the MI model. In this study, we found that the therapeutic effect of PLAC8 was related to the inhibition of the MEK/ERK signaling pathway by overexpression of PLAC8 and antagonism of the MEK/ERK signaling pathway. In conclusion, the inhibition of the MEK/ERK signaling pathway by PLAC8 under hypoxic conditions reduces apoptosis in H9c2 cells, which may provide new ideas for the determination and treatment of MI.
Insights
PLAC8 gene expression is reduced in myocardial infarction (MI) models, leading to increased cardiomyocyte apoptosis. Overexpressing PLAC8 inhibits the MEK/ERK pathway, offering a potential therapeutic strategy for MI.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Gene Expression Analysis
Background:
- Myocardial infarction (MI) incidence is rising, driven by cardiomyocyte apoptosis from reduced blood supply.
- Differential gene expression analysis identified PLAC8 as a key gene in MI pathogenesis.
Purpose of the Study:
- To investigate the role of PLAC8 in myocardial infarction.
- To elucidate the molecular mechanisms underlying PLAC8's function in MI.
- To explore PLAC8 as a potential therapeutic target for MI.
Main Methods:
- Myocardial infarction induced in mice via LAD ligation and in H9C2 cells via hypoxia.
- Histological analysis (HE, TTC, Tunel staining) to assess myocardial damage and apoptosis.
- Quantitative PCR and Western blotting to measure gene and protein expression (PLAC8, cle-Casp3, Bax).
- Investigation of MEK/ERK and P65 signaling pathways.
Main Results:
- MI models exhibited cardiomyocyte disorders, apoptosis, and inflammation.
- PLAC8 expression was significantly downregulated in MI models.
- Overexpression of PLAC8 attenuated apoptosis and reversed pathological changes.
- PLAC8's therapeutic effect correlated with MEK/ERK pathway inhibition.
Conclusions:
- PLAC8 plays a protective role in myocardial infarction by reducing cardiomyocyte apoptosis.
- Inhibition of the MEK/ERK signaling pathway is a key mechanism for PLAC8's protective effect.
- PLAC8 modulation presents a novel therapeutic avenue for myocardial infarction treatment.
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