Placental IL-1β inhibits PKM2 and leads to endothelial barrier injury in preeclampsia

Abstract

Preeclampsia, a life-threatening hypertensive disorder of pregnancy, continues to be a major global health concern. Maternal endothelial dysfunction induced by components from the impaired placenta is a key hallmark of preeclampsia (PE). Increased levels of IL-1β have been observed in preeclamptic placentas, but its association with endothelial dysfunction has remained uncertain. Our hypothesis was that IL-1β released from the placenta links the placental abnormalities with maternal endothelial dysfunction in PE. Our investigation revealed elevated levels of IL-1β in preeclampsia placentas, which were negatively correlated with reduced VE-Cadherin expression in endothelial cells, indicating consistent endothelial dysfunction. Moreover, we identified the glycolytic enzyme pyruvate kinase 2 (PKM2) as a key regulator of glycolysis involved in the regulation of junctional VE-Cadherin in endothelial cells. Rescue assays further demonstrated that the overexpression of PKM2 was necessary to ameliorate endothelial barrier injury induced by IL-1β. Our study provides novel insights into the molecular mechanisms driving preeclampsia, highlighting the regulatory roles of IL-1β, PKM2, and VE-Cadherin in endothelial cells. These identified interactions may play a crucial role in the pathogenesis of preeclampsia, offering potential targets for therapeutic interventions to preserve endothelial integrity and alleviate the condition. This project was funded by Natural Science Foundation of Shandong (ZR2022MH195 and ZR2023MH211), and the Graduate Student Research Grant from Weifang Medical University. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.