White Blood Cell Count-related Biomarkers for Acute Myocardial Infarction: Integrative Analysis of Mouse Models and Clinical Samples

INTRODUCTION: Although white blood cell count (WBC) is an accessible prognostic marker, the relationship between WBC-related genes and outcomes in acute myocardial infarction (AMI) remains unclear. METHODS: A retrospective study of 1,917 patients with AMI was conducted to estimate prognostic indicators. Mendelian randomization (MR) analysis was used to identify potential genes associated with the prognostic indicators, and the resulting genes were intersected with differentially expressed genes from the key monocyte subset identified in single-cell RNA sequencing (scRNA-seq) analyses. Key genes were screened by integrating 52 machine learning algorithms. The expression of key genes was validated by RT-qPCR with clinical samples. In addition, an AMI mouse model was established, and the expression of related proteins was further validated by western blotting and immunohistochemistry. RESULTS: Age, WBC, and serum potassium (K) level were identified as prognostic indicators for AMI. Eight key genes were identified. Gene set enrichment analysis (GSEA) showed that these genes were significantly enriched in immune- and inflammation-related pathways. RT-qPCR validation showed that the expression trends of five key genes (ITGA4, RASA3, ATG7, HSPA6, and ITGAM) were consistent with the bioinformatics results, whereas DSTN, FES, and MCL1 did not reach statistical significance. Additionally, WB and IHC further validated HSP70 family protein upregulation in the AMI mouse model. DISCUSSION: Eight AMI-related genes were identified and might contribute to disease progression through inflammatory regulation. The integration of multi-omics analysis and experimental validation underscores the translational potential of these genes. Although further experimental validation is warranted, these findings may offer novel insights for the development of therapeutic strategies for AMI. CONCLUSION: This study identified eight key WBC-related genes that may serve as potential biomarkers for AMI.