Abstract
Objective
Cardiovascular disorders constitute a substantial threat to global human health and safety. Of note, acute myocardial infarction (AMI), being a grave cardiovascular disorder, has garnered considerable attention owing to its elevated prevalence, mortality and broad demographic distribution. It is well established that hypoxia-induced apoptosis significantly contributes towards the onset and progression of AMI; however, several aspects regarding the biological indicators and molecular mechanisms of AMI remain elusive.
Method
This investigation utilized the Gene Expression Comprehensive (GEO) database to perform comprehensive analysis of pivotal genes employing techniques like differential analysis, Venn analysis, and weighted correlation network analysis (WGCNA). Subsequently, the correlation between the key genes and correlation factors was scrutinized, and the potential causal link between these factors and the outcome of AMI was probed via Mendelian randomization (MR). Additionally, real-time quantitative polymerase chain reaction (RT-qPCR) and lentivirus transfection experiments were executed, miRNA-mRNA networks were constructed utilizing miRBase databases, three-dimensional structures were predicted with the aid of RNAfold and Vfold3D databases, and drug sensitivity analysis was conducted using RNAactDrug databases.
Result
Following classification, WGCNA clustering, and Wien screening analysis, two distinctly expressed genes intimately linked to apoptosis - PTEN and BCL2L11 - were successfully identified. The outcomes of RT-qPCR and lentivirus infection experiments corroborated that the expression pattern of BCL2L11 conformed with our prior findings. Mendelian randomization analysis unveiled a robust causal relationship between BCL2L11 single nucleotide polymorphisms (SNPs) and AMI. Lastly, through miRNA-mRNA network and drug susceptibility analysis, it was discerned that the Ispinesib Mesylate, Bleomycin (50 uM)/miR-141-3p/BCL2L11 axis could potentially serve as efficacious therapeutic or preventive strategies against AMI.
Conclusion
In this study, we introduced the novel concepts of Ispinesib Mesylate and Bleomycin (50 uM)/miR-141-3p/BCL2L11 axis, offering a fresh perspective on the apoptotic mechanism in AMI.