Ambient fine particulate matter (PM2.5) was recognized as one of the most pressing environmental challenges confronting public health. There was a strong association between PM2.5 and pulmonary vascular diseases, the primary feature of which was pulmonary vascular remodeling. However, the underlying mechanisms by which PM2.5 induces pulmonary vascular remodeling have not been clarified. To address this gap, we established an environmental PM2.5-exposed mouse model and an in vitro cell model. Bioinformatics-based approaches were employed to identify potential regulators associated with pulmonary vascular remodeling, followed by an investigation into their potential roles in regulating pulmonary arterial function. Our results showed that PM2.5 exposure induced elevated pulmonary artery pressure and increased pulmonary artery wall thickness in mice. PM2.5 exposure induced cellular senescence in mouse pulmonary arterial endothelial cells (MPAECs) in vivo and in vitro, and PM2.5 treatment promoted mitochondrial dysfunction in MPAECs. Next, we used bioinformatics methods and experimental validation to identify MSC as potential regulator for mitochondrial dysfunction. And overexpression of MSC alleviated mitochondrial dysfunction-associated senescence (MiDAS) induced by PM2.5. In the mechanism, as a transcription factor, MSC regulated its downstream target gene NDUFB3, thereby facilitating PM2.5-induced MIDAS. This study offered novel insights into the molecular mechanisms underlying PM2.5-induced pulmonary vascular diseases and presented strategies for the precise intervention of pulmonary vascular injury triggered by atmospheric environmental factors.
