CD34 in preeclampsia: The role of endothelial cell pyroptosis and regulation by melatonin via melatonin membrane receptor 1

Preeclampsia (PE) is a serious clinical complication of pregnancy, whose etiology is remains poorly understood but is strongly linked to endothelial dysfunction. In this study, we have confirmed that low expression of CD34 is closely related to the pathogenesis of PE in PE patients, PE animal models, and endothelial cells. Reduced CD34 levels were found to exacerbate endothelial oxidative stress and induce inflammation-related endothelial pyroptosis in the placenta. Melatonin (MLT), a potent antioxidant, significantly attenuated endothelial oxidative damage. Most importantly MLT treatment significantly upregulated CD34 expression and downregulated proinflammatory cytokine levels in PE animal and cell models, thereby inhibiting pyroptosis. This activity of MLT is mediated by its membrane receptor MT1 (melatonin membrane receptor 1), as the effects were diminished by an MT1 blocker. The anti-inflammatory and antioxidant characteristics of MLT highlight its potential as a promising therapeutic candidate for PE.