Key result
Knockdown of Ccl9 promoted M2 macrophage polarization and reduced oxygen-glucose deprivation-induced cardiomyocyte injury in an acute myocardial infarction model.
Why the study?
Acute myocardial infarction is a major cause of sudden cardiac death and severe complications, making the identification of new therapeutic targets of great significance.
Ccl9 is a potential therapeutic target in acute myocardial infarction, as its knockdown promotes M2 macrophage polarization and reduces cardiomyocyte injury in preclinical models.
Background: Acute myocardial infarction (AMI) is one of the major causes of sudden cardiac death, resulting in severe complications. Therefore, it is of great significance to find new therapeutic targets. Methods: AMI datasets, Bulk RNA sequencing (Bulk RNA seq) GSE158157 and GSE23294, scRNA-seq GSE163129 datasets were downloaded from GEO. In this study, GSE163129 was subjected to dimensionality reduction analysis, subpopulation identification, enrichment analysis, and cellular communication analysis. Subsequently, we performed differential expression and immune infiltration analysis on GSE158157 and GSE23294 datasets to obtain seven monocyte/macrophage-related core genes. Finally, the mechanism of Ccl9 in AMI was explored through a series of animal and cellular experiments, which involved the establishment of AMI mouse model and isolation of primary mouse cardiomyocytes. Results: The t-distributed stochastic neighbor embedding (tSNE) analysis of GSE163129 identified 18 cell clusters, divided into six cell types. Monocytes and neutrophils were highly active. Differential expression analysis of GSE158157 and GSE23294 identified 2362 differentially expressed genes (DEGs). Immune infiltration analysis showed macrophage presence, with notable differences in M2 monocytes and other immune cells between AMI and Sham groups. Nine monocyte-associated hub genes were identified. qRT-PCR validation in AMI mouse models revealed significant upregulation of B2M, SPP1, Ccl4, LGALS3, MRC1, Ccl9, and FN1. Co-culture of primary cardiomyocytes and RAW264.7 cells indicated that low Ccl9 expression promoted M2 macrophage polarization and reduced OGD-induced cardiomyocyte injury. Conclusion: This study identified seven monocyte/macrophage-related genes in AMI and highlighted Ccl9's potential role in regulating M2 macrophage polarization and mitigating OGD-induced cardiomyocyte injury in AMI.
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Yang et al. (2025) studied Acute Myocardial Infarction. Ccl9 knockdown vs. Control/Sham was evaluated on Macrophage M2 polarization and cardiomyocyte injury (p=<0.05). Knockdown of Ccl9 promoted M2 macrophage polarization and reduced oxygen-glucose deprivation-induced cardiomyocyte injury in an acute myocardial infarction model.
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