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Clin Exp Pharmacol Physiol. 2019 Aug 26. doi: 10.1111/1440-1681.13169. [Epub ahead of print]

Effect of placental growth factor in models of experimental pre-eclampsia and trophoblast invasion.

Author information

1
Sydney Medical School, University of Sydney, Camperdown, New South Wales, Australia.
2
Vascular Immunology Group, Heart Research Institute, University of Sydney, Newtown, New South Wales, Australia.
3
School of Medicine, Western Sydney University, Campbelltown, New South Wales, Australia.
4
Nanoscale Organisation and Dynamics Group, Western Sydney University, Campbelltown, New South Wales, Australia.
5
Renal Department, Liverpool Hospital, Liverpool, New South Wales, Australia.

Abstract

Placental growth factor (PlGF) is decreased in early gestation of pregnant women who subsequently develop pre-eclampsia. In this study, pre-emptive treatment with PlGF to prevent pre-eclampsia was evaluated in an in vivo rodent model of experimental pre-eclampsia (EPE) induced by TNF-α and in an in vitro model of human first-trimester trophoblast invasion. Pregnant C57/BL6 mice were treated with recombinant mouse placental growth factor-2 (rmPlGF-2) 100 μg/kg/day IP from gestational day (gd) 10. Animals had EPE induced by continuous TNF-α infusion on gd 13 and were subject to either continuous blood pressure monitoring by radiotelemetry throughout pregnancy or live placenta T2 -weighted magnetic resonance imaging (MRI) to demonstrate placental function on gd 17. There was no difference in BP (P > .99), proteinuria (P = .9) or T2 values on MRI (P = .9) between control and rmPlGF-2-treated animals. On gd 13, animals treated with rmPlGF-2 demonstrated increased placenta PlGF (P = .01) and Toll-like receptor-3 (P = .03) mRNA expression as compared with controls. Fluorescent-labelled human uterine microvascular endothelial cells and HTR8/SVNeo cells were co-cultured on Matrigel and treated with recombinant human PlGF (rhPlGF) (10 ng/mL) and/or TNF-α (0.5 ng/mL). Trophoblast integration into endothelial networks was reduced by added TNF-α (P = .006), as was rhPlGF concentration in conditioned media (P < .0001). Cell integration was not ameliorated by addition of rhPlGF (P > .9). Although TNF-α-induced EPE was not reversed with pre-emptive rmPlGF-2, a further trial of pre-emptive rhPlGF in vivo is required to determine whether the absence of effect of rhPlGF demonstrated in vitro precludes PlGF as a preventative therapy for pre-eclampsia.

KEYWORDS:

placental MRI; placental growth factor; pre-eclampsia; trophoblast invasion

PMID:
31452230
DOI:
10.1111/1440-1681.13169

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