Hypoxia Upregulates the Notch3 Signaling Pathway to Promote Epithelial-Mesenchymal Transition in Pulmonary Artery Cells

Objective center dot To investigate the role and mechanism of Notch3 in a hypoxia-induced model of pulmonary hypertension, specifically pulmonary artery hypertension. Methods center dot A pulmonary artery hypertension rat model was induced using monocrotaline, and hepatic encephalopathy staining was used to observe the pathomorphological changes in pulmonary artery tissue. Primary isolation and extraction of rat pulmonary artery endothelial cells were performed, and a pulmonary artery hypertension cell model was established through hypoxia induction. Notch3 overexpression lentivirus (LV-Notch3) was used for intervention, and the expression of the Notch3 gene was detected using a real-time polymerase chain reaction. Western blotting was conducted to assess the expression of vascular endothelial growth factor, matrix metalloproteinase-2, and matrix metalloproteinase-9 proteins. Cell proliferation levels were measured using a medical training therapy assay. Results center dot Compared to the control group, the model group showed significant thickening of the pulmonary artery membrane, increased pulmonary angiogenesis, and endothelial cell damage. After Notch3 overexpression, the LV-Notch3 group showed further thickening of the pulmonary artery tunica media, increased pulmonary angiogenesis, and significantly improved endothelial cell injury. Compared to control cells, the model group showed a significant decrease in Notch3 expression (P< .05), while the expression levels of vascular endothelial growth factor, MMP-2, and MMP-9 proteins and cell proliferation ability increased significantly (P < .05). Following Notch3 overexpression, there was a significant increase in Notch3 expression (P < .05), and the expression levels of vascular endothelial growth factor, MMP-2, and MMP-9 proteins, as well as cell proliferation ability decreased significantly (P < .05). Conclusions center dot Notch3 can potentially reduce angiogenesis and proliferation in pulmonary artery endothelial cells and improve hypoxia-induced pulmonary artery hypertension in rats.