Unveiling the molecular impact of pulmonary embolism on the right ventricle: a multi-layer transcriptomic study in a porcine model.

Venous thromboembolism (VTE) is a prevalent and potentially fatal condition, typically initiating deep vein thrombosis (DVT). Subsequent embolization can lead to pulmonary embolism (PE), a significant threat to cardiovascular function. Approximately 5% of PE cases result in sudden cardiac arrest due to acute right ventricular failure, arrhythmias, and circulatory shock. Given the considerable influence of PE on right ventricular function, this study aimed to investigate alterations in gene expression within the right ventricle associated with PE in a porcine model. The study was performed on 12 male pigs, divided into two groups of six animals each. In the experimental group, a thrombus was induced in the right femoral vein of each animal and subsequently released to induce pulmonary embolism. The remaining six animals served as a control group. Right ventricular myocardial samples were collected for subsequent transcriptomic and immunohistochemical analyses. In the experimental group, tissue samples were taken 24 h post-thrombus release to characterize changes typical of acute PE. Multistep bioinformatics identified 1992 significantly differentiating molecules: 1436 differentially expressed genes (DEGs), 308 differentially expressed lncRNAs (DELs), and 248 other RNA species. Among these, 417 DEGs, 101 DELs, and 58 other RNAs were downregulated, while 1019 DEGs, 207 DELs, and 190 other RNAs were upregulated. Gene Ontology (GO) analysis assigned molecules to 259 processes (184 biological, 37 cellular, 33 molecular), indicating active inflammatory and immune signaling in cardiac tissue, suggesting roles in ventricular remodeling and stress response. KEGG pathway analysis highlighted altered Oxytocin signaling and Complement and coagulation cascades in PE hearts. Splicing analysis revealed 55,950 alternative splicing events in Sus scrofa right ventricles (PE vs. CTR). Additionally, 3142 single nucleotide variants (SNVs) were identified. This study presents the first comprehensive analysis of right ventricular gene expression profiles in response to PE. The findings indicate that alterations in the oxytocin signaling pathway, the complement and coagulation cascades, and disturbed inflammatory and immune signaling are critically involved in the pathogenesis of right ventricular dysfunction during PE.