Placental IL‐1β impairs endothelial functions by reducing VE‐cadherin expression in PE

Abstract

Preeclampsia (PE) is a pregnancy‐specific syndrome that affects 5~8% pregnancies and is a leading cause of maternal and neonatal morbidity and mortality, especially in low‐income and middle‐income countries. Widespread systemic inflammation and endothelial dysfunction are hallmarks of injury in PE, however, the molecular mechanisms linking inflammation and endothelial dysfunction remain largely unknown. We tested the hypothesis that placental IL‐1β impairs endothelial functions by inhibiting VE‐cadherin expression in PE. We found that NLRP3 inflammasome was overactivated in preeclamptic placenta, which induced more IL‐1β release. We also observed that IL‐1β significantly increased endothelial permeability of Human Umbilical Vein Endothelial Cells (HUVECs) in a dose‐response manner, and inhibition of IL‐1β receptor significantly attenuated the increase of endothelial permeability induced by IL‐1β. We further revealed that both mRNA and protein level of VE‐cadherin was reduced by IL‐1β in HUVECs. and overexpression of VE‐cadherin in endothelial cells reversed IL‐1β‐induced increase in endothelial permeability. Taken together, our preliminary data suggested that excessive placental IL‐1β significantly impaired endothelial functions by inhibiting VE‐cadherin expression.