title: Placental expression of the angiogenic placental growth factor is stimulated by both aldosterone and simulated starvation.
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.
authors.affiliation: Department of Nephrology, Hypertension and Clinical Pharmacology, University of Bern, 3010 Berne, Switzerland; Department of Clinical Research, University of Bern, 3010 Berne, Switzerland.
authors.forename: Nicole
authors.initials: N
authors.lastname: Eisele
authors.affiliation: Institute for Biochemistry and Molecular Medicine, University of Bern, 3010 Berne, Switzerland; Swiss National Center of Competence in Research, NCCR TransCure, University of Bern, 3010 Berne, Switzerland.
authors.forename: Christiane
authors.initials: C
authors.lastname: Albrecht
authors.affiliation: Department of Nephrology, Hypertension and Clinical Pharmacology, University of Bern, 3010 Berne, Switzerland; Department of Clinical Research, University of Bern, 3010 Berne, Switzerland.
authors.forename: Hiten D
authors.initials: HD
authors.lastname: Mistry
authors.affiliation: Department of Nephrology, Hypertension and Clinical Pharmacology, University of Bern, 3010 Berne, Switzerland; Department of Clinical Research, University of Bern, 3010 Berne, Switzerland.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Dick
authors.affiliation: Department of Obstetrics and Gynecology, University Hospital Bern, University of Bern, 3010 Berne, Switzerland; Swiss National Center of Competence in Research, NCCR TransCure, University of Bern, 3010 Berne, Switzerland.
authors.forename: Marc
authors.initials: M
authors.lastname: Baumann
authors.affiliation: Department of Obstetrics and Gynecology, University Hospital Bern, University of Bern, 3010 Berne, Switzerland; Swiss National Center of Competence in Research, NCCR TransCure, University of Bern, 3010 Berne, Switzerland.
authors.forename: Daniel
authors.initials: D
authors.lastname: Surbek
authors.affiliation: Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Gemma
authors.initials: G
authors.lastname: Currie
authors.affiliation: Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.
authors.forename: Christian
authors.initials: C
authors.lastname: Delles
authors.affiliation: Department of Nephrology, Hypertension and Clinical Pharmacology, University of Bern, 3010 Berne, Switzerland; Department of Clinical Research, University of Bern, 3010 Berne, Switzerland. Electronic address: markus.mohaupt@insel.ch.
authors.forename: Markus G
authors.initials: MG
authors.lastname: Mohaupt
authors.affiliation: Department of Nephrology, Hypertension and Clinical Pharmacology, University of Bern, 3010 Berne, Switzerland; Department of Clinical Research, University of Bern, 3010 Berne, Switzerland.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Escher
authors.affiliation: Department of Nephrology, Hypertension and Clinical Pharmacology, University of Bern, 3010 Berne, Switzerland; Department of Clinical Research, University of Bern, 3010 Berne, Switzerland.
authors.forename: Carine
authors.initials: C
authors.lastname: Gennari-Moser
mesh_terms: D000328:Adult; D000450:Aldosterone / Q000378:metabolism*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D010920:Placenta / Q000378:metabolism*; D000072483:Placenta Growth Factor / Q000378:metabolism*; D011247:Pregnancy; D013217:Starvation / Q000378:metabolism
chemical_list: D000072483:Placenta Growth Factor; D000450:Aldosterone
keywords: Aldosterone; Glucose; Placental growth factor; Pregnancy; Trophoblast