A Dysregulation of the Prolactin/Vasoinhibin Axis Appears to Contribute to Preeclampsia

Abstract

Preeclampsia is a hypertensive disorder affecting 3-5% of all pregnancies. The only curative treatment is delivery of the placenta and the pathophysiology is poorly understood. Studies have demonstrated altered levels of antiangiogenic factors in patients with preeclampsia. One such factor is the antiangiogenic and antivasodilatatory peptide hormone vasoinhibin, which is higher in the circulation, urine, and amniotic fluid of women with preeclampsia. Normal pregnancy is characterized by elevated circulating prolactin and placental lactogen levels, both of which can serve as vasoinhibin precursors when they are enzymatically cleaved. A dysregulation of vasoinhibin generation during preeclampsia is indicated by higher vasoinhibin, prolactin, placental lactogen, and vasoinhibin-generating enzymes levels and activity. The present article integrates known vasoinhibin levels, effects, and signaling mechanisms to the clinical characteristics of preeclampsia to substantiate the notion that vasoinhibin dysregulation can be causally linked to the development of preeclampsia. If this view is demonstrated, assessment of vasoinhibin levels and regulation of its activity could help estimate the risk of preeclampsia and improve its treatment.

Deepening the knowledge of rare diseases dependent on angiogenesis through semantic similarity clustering and network analysis

“…We also check in the current bibliography its relationship with angiogenesis. For example, the terms HP: ‘Seizure’, HP: ‘Headache’ and HP: ‘Hypertension’ are quite related to endothelial dysfunctions in patients with preeclampsia and hypertensive encephalopathy, and have been associated with dysregulations of vascular endothelial growth factor (VEGF) in endothelial cells [ 20 , 22 , 26 ]. In fact, there are studies that relates VEGF-induced angiogenesis and the phenotypes HP: ‘Hepatomegaly’, HP: ‘Splenomegaly’ and HP: ‘Thrombocytopenia’ [ 57 , 58 ].…”

Supraphysiological Role of Melatonin Over Vascular Dysfunction of Pregnancy, a New Therapeutic Agent?

“…Moreover, the impaired invasion of the uterine wall by trophoblast induce hypoxia, and produce a modification of placental secretion of critical angiogenic and antiangiogenic factors such as vascular endothelial growth factor (VEGF) ( Frigato et al, 2009 ) and Placental lactogen (PL-II) member of the prolactin gene family. These vascular factors and their impaired secretion have been proposed to predict risk during pregnancy ( Wang and Zhao, 2010 ; Valenzuela et al, 2012 ; Lenke et al, 2019 ). Besides, VEGF and placental growth factor (PlGF) induce placental angiogenesis via activation of VEGFR-1/Flt-1 and VEGFR-2/KDR, and both factors increase endothelial cell adhesion, chemotaxis and increase angiogenesis ( Helske et al, 2001 ; Poniedziałek-Czajkowska et al, 2021 ).…”

Immunometric and functional measurement of endogenous vasoinhibin in human sera

“…The antiangiogenic protein hormone vasoinhibin, which is generated by the proteolytic cleavage of prolactin (PRL), is of interest in the context of various diseases, including vasoproliferative retinopathies and diabetic macular oedema ( 1 , 2 ), peripartum cardiomyopathy ( 3 – 5 ), preeclampsia ( 6 – 8 ), inflammatory arthritis ( 9 , 10 ), and cancer ( 11 , 12 ). The interest is mainly due to the vascular actions of vasoinhibin, which include the inhibition of endothelial cell proliferation, vasodilation, and vasopermeability, all relevant in the above mentioned diseases ( 13 ).…”

“…The presence of the placenta, as opposed to the fetus, is essential for the development of preeclampsia; the shedding of antiangiogenic factors from the placenta into the maternal circulation contributes to maternal endothelial dysfunction ( 26 ). Clinical studies have reported increased levels of vasoinhibin in the circulation, urine, and amniotic fluid of patients with preeclampsia, and suggested that it may contribute to endothelial cell dysfunction in preeclampsia ( 6 – 8 , 27 ). In this context, the chick chorioallantoic membrane (CAM) angiogenesis assay is a relevant model.…”