Targeting the vascular dysfunction: Potential treatments for preeclampsia

Abstract

Preeclampsia is a pregnancy-specific disorder clinically characterized by new-onset hypertension (>20 weeks' gestation) with one or more of proteinuria and maternal organ dysfunction such as renal insufficiency, liver dysfunction, neurological complications, fetal growth restriction, or uteroplacental dysfunction. 1,2 Each year, preeclampsia is the principal cause of death in over 60 000 women and in more than 500 000 babies globally. 3 The pathophysiological mechanisms underlying the disease are still not entirely clear. Briefly, In 2017, Sarah was awarded her PhD at the University of Melbourne, Australia, and is currently an NHMRC Peter Doherty Research Fellow in the Department of Obstetrics and Gynecology at Monash University, Australia. The focus of her research is to assess the potential of new and old therapeutics to target the vascular dysfunction of preeclampsia, and translate these studies into clinical application. AbstractPreeclampsia is a pregnancy-specific disorder, primarily characterized by new-onset hypertension in combination with a variety of other maternal or fetal signs. The pathophysiological mechanisms underlying the disease are still not entirely clear.Systemic maternal vascular dysfunction underlies the clinical features of preeclampsia. It is a result of oxidative stress and the actions of excessive anti-angiogenic factors, such as soluble fms-like tyrosine kinase, soluble endoglin, and activin A, released by a dysfunctional placenta. The vascular dysfunction then leads to impaired regulation and secretion of relaxation factors and an increase in sensitivity/production of constrictors. This results in a more constricted vasculature rather than the relaxed vasodilated state associated with normal pregnancy. Currently, the only effective "treatment" for preeclampsia is delivery of the placenta and therefore the baby.Often, this means a preterm delivery to save the life of the mother, with all the attendant risks and burdens associated with fetal prematurity. To lessen this burden, there is a pressing need for more effective treatments that target the maternal vascular dysfunction that underlies the hypertension. This review details the vascular effects of key drugs undergoing clinical assessment as potential treatments for women with preeclampsia.

MicroRNA‐210 regulates human trophoblast cell line HTR‐8/SVneo function by attenuating Notch1 expression: Implications for the role of microRNA‐210 in pre‐eclampsia

“…Pre‐eclampsia is a severe hypertensive complication characterized by hypertension and the involvement of one or more other organ systems or the fetus, such as liver dysfunction, renal insufficiency, thrombocytopenia, new emerging neurological complications, or fetal growth restriction (Marshall, Cox, Parry, & Wallace, ). However, the fundamental cause and pathogenesis of pre‐eclampsia are still not well known.…”

Activin A is Not a Reliable Prognostic Biomarker For Bilirubin Induced Neurotoxicity in Neonates

“…It could be that brain insults that involve ischemic vascular injury rather than neuronal injury are the stimulators for increased activin A (28), therefore the pathophysiology of bilirubin induced brain injury which does not induce these ischemic changes may be the reason that activin A levels do not significantly increase in neonatal hyperbilirubinemia. Additionally, other factors exist that may affect activin A levels, including different maternal factors (29,30) as well as varying gestational (31) and post-natal ages (28).…”

The Plasma Level of Soluble Endoglin in Hypertensive Patients Undergoing Long-Term Treatment With Candesartan

“…Diastolic BP was found to be a protective factor for sEng in group B (Table III). sEng has been linked to hypertension and preeclampsia [1,32,47]. Hypoxia has been reported to induce the formation of reactive oxygen species, which can convert cholesterol to oxysterol species that bind to liver/retinoid X receptors and, thus, increase the plasma level of MMP-13 and decrease the level of tissue inhibitor of metalloproteinase-3.…”