Serpine1 mediates cardiac fibrosis following myocardial ischemia-reperfusion injury by activating the endothelial-mesenchymal transition process and inducing mitochondrial damage

Background: Cardiac fibrosis represents a severe pathological consequence following myocardial ischemia-reperfusion (MI/R) injury. This study aims to investigate the underlying molecular mechanisms of Serpine1 in post-MI/R cardiac fibrosis, with the ultimate goal of identifying potential therapeutic targets for alleviating disease progression. Methods: Bioinformatics approaches were utilized to identify potential therapeutic target genes. To investigate the functional role of the target gene, we established stable gene-silenced cell models using RNA interference technology. For functional characterization, cell proliferation viability was assessed using the CCK-8 assay, while apoptotic rates were quantitatively analyzed through TUNEL staining. Mitochondrial membrane potential was determined using JC-1 fluorescent probe detection. To elucidate the underlying molecular mechanisms, we performed quantitative real-time PCR (qPCR) to measure mRNA expression levels of relevant genes and conducted Western blot analysis to evaluate the expression profiles of target proteins. In addition, we confirmed the function of Serpine1 in an in vivo model. Results: Serpine1 has been successfully identified as a critical target gene for therapeutic intervention in cardiac fibrosis following MI/R injury. Through comprehensive bioinformatics analysis and in vitro experimental validation, we observed a significant upregulation of Serpine1 expression in MI/R cell models. At the molecular level, overexpression of Serpine1 activates the endothelial-to-mesenchymal transition (EndMT) process, exacerbates mitochondrial dysfunction, leading to decreased cell viability and enhanced cellular apoptosis. Specifically, Serpine1 overexpression markedly downregulated the expression of endothelial phenotype markers (including CD31 and VE-cadherin), while simultaneously upregulating mesenchymal markers (such as α-SMA and vimentin). Conclusion: This study elucidates the pivotal regulatory mechanisms of Serpine1 in the progression of cardiac fibrosis following MI/R injury. Our findings provide novel insights into the pathophysiological mechanisms underlying cardiac fibrosis and establish a crucial molecular foundation for the development of targeted therapeutic strategies.