Pre-eclampsia: pathogenesis, novel diagnostics and therapies

Abstract

Pre-eclampsia is a complication of pregnancy that is associated with substantial maternal and fetal morbidity and mortality. The disease presents with new-onset hypertension and often proteinuria in the mother, which can progress to multi-organ dysfunction, including hepatic, renal and cerebral disease, if the fetus and placenta are not delivered. Maternal endothelial dysfunction due to circulating factors of fetal origin from the placenta is a hallmark of pre-eclampsia. Risk factors for the disease include maternal comorbidities, such as chronic kidney disease, hypertension and obesity; a family history of pre-eclampsia, nulliparity or multiple pregnancies; and previous preeclampsia or intrauterine fetal growth restriction. In the past decade, the discovery and characterization of novel antiangiogenic pathways have been particularly impactful both in increasing understanding of the disease pathophysiology and in directing predictive and therapeutic efforts. In this Review, we discuss the pathogenic role of antiangiogenic proteins released by the placenta in the development of pre-eclampsia and review novel therapeutic strategies directed at restoring the angiogenic imbalance observed during pre-eclampsia. We also highlight other notable advances in the field, including the identification of long-term maternal and fetal risks conferred by pre-eclampsia.

Maternal plasma proteomics in a rat model of pregnancy complications reveals immune and pro‐coagulant gene pathway activation

“…In contrast, we observed a significant decrease in the pro-inflammatory cytokine profile in LEW dams throughout pregnancy that is associated with better reproductive outcomes. 22,24 Other studies have observed a significant interaction of HP genotype with recurrent miscarriage and pre-eclampsia. [17][18][19] HP is an anti-oxidant protein that binds free hemoglobin and is therefore increased during inflammation or decreased in the presence of hemolysis.…”

“…[20][21][22] This is of great importance because obesity can induce additional physiological and gene dysregulation. 22,24 Other studies have observed a significant interaction of HP genotype with recurrent miscarriage and pre-eclampsia. 24,25 The plasticity of HP could explain the different results in various human proteomic studies where pre-eclampsia or recurrent miscarriage has been associated with either increased or decreased HP and HBB.…”

“…22,24 Other studies have observed a significant interaction of HP genotype with recurrent miscarriage and pre-eclampsia. 24,25 The plasticity of HP could explain the different results in various human proteomic studies where pre-eclampsia or recurrent miscarriage has been associated with either increased or decreased HP and HBB. 21,23,[26][27][28] Finally, BN rats had lower levels of TTR, a negative acute phase protein whose function is to transport thyroid hormones (T4) and…”

“…The increased pro-inflammatory cytokine profile (ie, increased IL6 and IFNγ, and decreased IL10) in pregnant BN dams correlates with increases in circulating levels of acute-phase proteins such as CRP, F2, and C4 which are known to increase during chronic "cold" (ie, non-infectious) inflammatory diseases. 24,25 The plasticity of HP could explain the different results in various human proteomic studies where pre-eclampsia or recurrent miscarriage has been associated with either increased or decreased HP and HBB. Therefore, lower plasma HP in pregnant BN rats could correlate with increased ROS or increased hemolysis.…”

Down‐regulated lncRNA AGAP2‐AS1 contributes to pre‐eclampsia as a competing endogenous RNA for JDP2 by impairing trophoblastic phenotype

“…Currently, PE is considered to be a multisystem syndrome of human gestation and is related to high maternal and infant morbidity and mortality rates . Pregnancy predisposes females to a higher risk of pulmonary oedema, hepatic and renal failure, seizures, cerebral haemorrhage and even death . Additionally, PE can impact the overall health and well‐being of the foetus.…”