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 <i>DLL4</i>, which showed the highest distinguishing efficiency between PAH and control samples. Functional and pathway enrichment analyses revealed the involvement of <i>DLL4</i> in critical biological processes and pathways related to PAH, including notch signaling, immune cell function, and inflammatory responses. Further investigation demonstrated that decreased <i>DLL4</i> expression correlated with increased M2 macrophage polarization, suggesting a potential role for <i>DLL4</i> 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 <i>DLL4</i> 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.