Mitophagy-associated biomarkers and macrophage involvement in pulmonary arterial hypertension: identification and functional implications.

Background: Pulmonary arterial hypertension (PAH) is a progressive disorder characterized by pulmonary vascular remodeling and mitochondrial dysfunction. Recent studies have implicated impaired mitophagy in the pathogenesis of PAH; however, the underlying mechanisms and associated biomarkers remain insufficiently defined. This study used an integrative approach, incorporating bulk transcriptomic profiling, single-cell RNA sequencing (scRNA-seq), machine learning algorithms, and experimental validation to explore the relationship between mitophagy and PAH. Methods: Differentially expressed genes were extracted from publicly available microarray datasets and intersected with mitophagy-related genes curated from the MitoCarta 3.0 database. Weighted gene co-expression network analysis, along with five distinct machine learning models, identified five candidate mitophagy-associated biomarkers: Results and Conclusion: The findings underscore the involvement of mitophagy in the pathobiology of PAH and identify five macrophage-associated biomarkers with strong diagnostic potential. These results may inform future strategies aimed at early detection and targeted therapeutic interventions in PAH.