Increased Placental sFLT1 (Soluble fms-Like Tyrosine Kinase Receptor-1) Drives the Antiangiogenic Profile of Maternal Serum Preceding Preeclampsia but Not Fetal Growth Restriction.
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Authors
Cook, Emma
Publication Date
2023-02Journal Title
Hypertension
ISSN
0194-911X
Publisher
Ovid Technologies (Wolters Kluwer Health)
Type
Article
This Version
AM
Metadata
Show full item recordCitation
Gaccioli, F., Sovio, U., Gong, S., Cook, E., Charnock-Jones, D. S., & Smith, G. C. (2023). Increased Placental sFLT1 (Soluble fms-Like Tyrosine Kinase Receptor-1) Drives the Antiangiogenic Profile of Maternal Serum Preceding Preeclampsia but Not Fetal Growth Restriction.. Hypertension https://doi.org/10.1161/HYPERTENSIONAHA.122.19482
Abstract
BACKGROUND: Preeclampsia and fetal growth restriction (FGR) are both associated with an increased ratio of sFLT1 (soluble fms-like tyrosine kinase-1) to PlGF (placenta growth factor) in maternal serum. In preeclampsia, it is assumed that increased placental release of sFLT1 results in PlGF being bound and inactivated. However, direct evidence for this model is incomplete, and it is unclear whether the same applies in FGR. METHODS: We conducted a prospective cohort study where we followed 4212 women having first pregnancies from their dating ultrasound, obtained blood samples serially through the pregnancy, and performed systematic sampling of the placenta after delivery. The aim of the present study was to determine the relationship between protein levels of sFLT1 and PlGF in maternal serum measured at ≈36 weeks and placental tissue lysates obtained after term delivery in 82 women with preeclampsia, 50 women with FGR, and 132 controls. RESULTS: The sFLT1:PlGF ratio was increased in both preeclampsia and FGR in both the placenta and maternal serum. However, in preeclampsia, the maternal serum ratio of sFLT1:PlGF was strongly associated with placental sFLT1 level (r=0.45; P<0.0001) but not placental PlGF level (r=-0.17; P=0.16). In contrast, in FGR, the maternal serum ratio of sFLT1:PlGF was strongly associated with placental PlGF level (r=-0.35; P=0.02) but not sFLT1 level (r=0.04; P=0.81). CONCLUSIONS: We conclude that the elevated sFLT1:PlGF ratio is primarily driven by increased placental sFLT1 in preeclampsia, whereas in FGR, it is primarily driven by decreased placental PlGF.
Keywords
cohort studies, fetal growth retardation, placenta, placenta growth factor, preeclampsia, Pregnancy, Female, Humans, Pre-Eclampsia, Prospective Studies, Vascular Endothelial Growth Factor Receptor-1, Placenta Growth Factor, Vascular Endothelial Growth Factor A, Receptor Protein-Tyrosine Kinases, Biomarkers
Sponsorship
The work was supported by the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre (Women’s Health theme), and grants from the Medical Research Council (United Kingdom; MR/K021133/1), and supported by the NIHR Cambridge Clinical Research Facility.
Funder references
Cambridge University Hospitals NHS Foundation Trust (CUH) (146281)
Medical Research Council (MR/K021133/1)
Identifiers
External DOI: https://doi.org/10.1161/HYPERTENSIONAHA.122.19482
This record's URL: https://www.repository.cam.ac.uk/handle/1810/338135
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