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

Eisele, N. et al. (2016) Placental expression of the angiogenic placental growth factor is stimulated by both aldosterone and simulated starvation. Placenta, 40, pp. 18-24. (doi: 10.1016/j.placenta.2016.02.004) (PMID:27016778)

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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:Articles
Additional Information:This research was supported by the Swiss National Foundation (personal grant 32-135596 to MGM and 310030_149958 to CA) and the Swiss National Center of Competence in Research, NCCR TransCure (CA). HDM is supported by an ERA-EDTA Fellowship (LTF 137-2013). CD is supported by grants from the European Union (EUMASCARA; project reference 278249) and the Chief Scientist Office (reference ETM/196).
Glasgow Author(s) Enlighten ID:Currie, Dr Gemma and Delles, Professor Christian
Authors: Eisele, N., Albrecht, C., Mistry, H. D., Dick, B., Baumann, M., Surbek, D., Currie, G., Delles, C., Mohaupt, M. G., Escher, G., and Gennari-Moser, C.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:Placenta
ISSN (Online):1532-3102

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
595241Cardiovascular consequences of preeclampsia in women from the Generation Scotland: Scottish Family Health Study.Christian DellesScottish Executive Health Department (SEHHD-CSO)ETM/196RI CARDIOVASCULAR & MEDICAL SCIENCES