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

Eisele, Nicole and Albrecht, Christiane and Mistry, Hiten D. and Dick, Bernhard and Baumann, Marc and Surbeck, Daniel and Currie, Gemma and Delles, Christian and Mohaupt, Markus and Escher, Genevieve and Gennari-Moser, Carine (2016) Placental expression of the angiogenic placental growth factor is stimulated by both aldosterone and simulated starvation. Placenta, 40 . pp. 18-24. ISSN 1532-3102

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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.

Item Type: Article
Keywords: Aldosterone; Placental growth factor; Pregnancy; Glucose; Trophoblast
Schools/Departments: University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Medicine > Division of Child Health, Obstetrics and Gynaecology
Identification Number: 10.1016/j.placenta.2016.02.004
Depositing User: Mistry, Hiten
Date Deposited: 21 Jul 2017 10:43
Last Modified: 21 Jul 2017 10:53
URI: http://eprints.nottingham.ac.uk/id/eprint/44334

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