Inhibition of DLL4/Notch Signaling Pathway Promotes M2 Polarization and Cell Proliferation in Pulmonary Arterial Hypertension.

In this study, we conducted a comprehensive analysis to identify key genes and pathways associated with pulmonary arterial hypertension (PAH) and investigated the role of delta-like ligand 4 (DLL4) in PAH pathogenesis. Through integrated analysis of multiple data sets, we identified 6 candidate differentially expressed genes (DEGs), notably , which showed the highest distinguishing efficiency between PAH and control samples. Functional and pathway enrichment analyses revealed the involvement of in critical biological processes and pathways related to PAH, including notch signaling, immune cell function, and inflammatory responses. Further investigation demonstrated that decreased expression correlated with increased M2 macrophage polarization, suggesting a potential role for in preventing M2 differentiation. Additionally, the DLL4/Notch1 axis was found to influence the Notch profile and regulate signaling mediators during M2 differentiation. These findings highlight as a promising biomarker and therapeutic target for PAH, shedding light on the underlying molecular mechanisms and providing insights for the development of novel treatment strategies.