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Placental expression of the angiogenic placental growth factor is stimulated by both aldosterone and simulated starvation

Eisele, Nicole; Albrecht, Christiane; Mistry, Hiten D.; Dick, Bernhard; Baumann, Marc; Surbeck, Daniel; Currie, Gemma; Delles, Christian; Mohaupt, Markus; Escher, Genevieve; Gennari-Moser, Carine

Authors

Nicole Eisele

Christiane Albrecht

Hiten D. Mistry hiten.mistry@nottingham.ac.uk

Bernhard Dick

Marc Baumann

Daniel Surbeck

Gemma Currie

Christian Delles

Markus Mohaupt

Genevieve Escher

Carine Gennari-Moser



Abstract

Aldosterone is an important factor supporting placental growth and fetal development. Recently, expression of placental growth factor (PlGF) has been observed in response to aldosterone exposure in different models of atherosclerosis. Thus, we hypothesized that aldosterone up-regulates growth-adaptive angiogenesis in pregnancy, via increased placental PlGF expression.

We followed normotensive pregnant women (n = 24) throughout pregnancy and confirmed these results in a second independent first trimester cohort (n = 36). Urinary tetrahydroaldosterone was measured by gas chromatography-mass spectrometry and corrected for creatinine. Circulating PlGF concentrations were determined by ELISA. Additionally, cultured cell lines, adrenocortical H295R and choriocarcinoma BeWo cells, as well as primary human third trimester trophoblasts were tested in vitro. PlGF serum concentrations positively correlated with urinary tetrahydroaldosterone corrected for creatinine in these two independent cohorts. This observation was not due to PlGF, which did not induce aldosterone production in cultured H295R cells. On the other hand, PlGF expression was specifically enhanced by aldosterone in the presence of forskolin (p < 0.01) in trophoblasts. A pronounced stimulation of PlGF expression was observed with reduced glucose concentrations simulating starvation (p < 0.001).

In conclusion, aldosterone stimulates placental PlGF production, enhancing its availability during human pregnancy, a response amplified by reduced glucose supply. Given the crucial role of PlGF in maintaining a healthy pregnancy, these data support a key role of aldosterone for a healthy pregnancy outcome.

Journal Article Type Article
Publication Date Apr 1, 2016
Journal Placenta
Print ISSN 0143-4004
Electronic ISSN 1532-3102
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 40
APA6 Citation Eisele, N., Albrecht, C., Mistry, H. D., Dick, B., Baumann, M., Surbeck, D., …Gennari-Moser, C. (2016). Placental expression of the angiogenic placental growth factor is stimulated by both aldosterone and simulated starvation. Placenta, 40, https://doi.org/10.1016/j.placenta.2016.02.004
DOI https://doi.org/10.1016/j.placenta.2016.02.004
Keywords Aldosterone; Placental growth factor; Pregnancy; Glucose; Trophoblast
Publisher URL http://www.sciencedirect.com/science/article/pii/S0143400416300248
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by-nc-nd/4.0

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2016-02-01 Manuscript PlGF_Final rev HDM.pdf (406 Kb)
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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by-nc-nd/4.0





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