The Potential for Placental Activation of PPARγ to Improve the Angiogenic Profile in Preeclampsia

Preeclampsia (PE) is one of the most common causes of maternal-fetal morbidity and mortality world-wide. While the underlying causes of PE remain elusive, aberrant trophoblast differentiation and function are thought to cause an imbalance of secreted angiogenic proteins resulting in systemic endothelial dysfunction and organ damage in the mother. The placental dysfunction is also characterized by a reduction of the transcription factor, peroxisome proliferator activated receptor gamma (PPAR gamma) which normally promotes trophoblast differentiation and healthy placental function. This study aimed to understand how placental activation of PPAR gamma effects the secretion of angiogenic proteins and subsequently endothelial function. To study this, healthy and PE placental tissues were cultured with or without the PPAR gamma agonist, Rosiglitazone, and a Luminex assay was performed to measure secreted proteins from the placenta. To assess the angiogenic effects of placental activation of PPAR gamma, human umbilical vein endothelial cells (HUVECs) were cultured with the placental conditioned media and the net angiogenic potential of these cells was measured by a tube formation assay. This is the first study to show PPAR gamma's beneficial effect on the angiogenic profile in the human preeclamptic placenta through the reduction of anti-angiogenic angiopoietin-2 and soluble endoglin and the upregulation of pro-angiogenic placental growth factor, fibroblast growth factor-2, heparin-binding epidermal growth factor, and follistatin. The changes in the angiogenic profile were supported by the increased angiogenic potential observed in the HUVECs when cultured with conditioned media from rosiglitazone-treated preeclamptic placentas. The restoration of these disrupted pathways by activation of PPAR gamma in the preeclamptic placenta offers potential to improve placental and endothelial function in PE.

Automated summary

Preeclampsia (PE) is a major cause of maternal-fetal morbidity and mortality worldwide. This research shows that placental activation of PPAR gamma can improve the secretion of angiogenic proteins and enhance endothelial function in PE.