TY - JOUR
T1 - Alterations of Placental Sodium in Preeclampsia
T2 - Trophoblast Responses
AU - Mistry, Hiten D.
AU - Klossner, Rahel
AU - Scaife, Paula J.
AU - Eisele, Nicole
AU - Kurlak, Lesia O.
AU - Kallol, Sampada
AU - Albrecht, Christiane
AU - Gennari-Moser, Carine
AU - Briggs, Louise V.
AU - Broughton Pipkin, Fiona
AU - Mohaupt, Markus G.
N1 - Publisher Copyright:
© 2024 The Authors.
PY - 2024/9/1
Y1 - 2024/9/1
N2 - BACKGROUND: Evidence suggests that increasing salt intake in pregnancy lowers blood pressure, protecting against preeclampsia. We hypothesized that sodium (Na+) evokes beneficial placental signals that are disrupted in preeclampsia. METHODS: Blood and urine were collected from nonpregnant women of reproductive age (n=26) and pregnant women with (n=50) and without (n=55) preeclampsia, along with placental biopsies. Human trophoblast cell lines and primary human trophoblasts were cultured with varying Na+ concentrations. RESULTS: Women with preeclampsia had reduced placental and urinary Na+ concentrations, yet increased urinary angiotensinogen and reduced active renin, aldosterone concentrations, and osmotic response signal TonEBP (tonicity-responsive enhancer binding protein) expression. In trophoblast cell cultures, TonEBP was consistently increased upon augmented Na+ exposure. Mechanistically, inhibiting Na+/K+-ATPase or adding mannitol evoked the TonEBP response, whereas inhibition of cytoskeletal signaling abolished it. CONCLUSIONS: Enhanced Na+ availability induced osmotic gradient-dependent cytoskeletal signals in trophoblasts, resulting in proangiogenic responses. As placental salt availability is compromised in preeclampsia, adverse systemic responses are thus conceivable.
AB - BACKGROUND: Evidence suggests that increasing salt intake in pregnancy lowers blood pressure, protecting against preeclampsia. We hypothesized that sodium (Na+) evokes beneficial placental signals that are disrupted in preeclampsia. METHODS: Blood and urine were collected from nonpregnant women of reproductive age (n=26) and pregnant women with (n=50) and without (n=55) preeclampsia, along with placental biopsies. Human trophoblast cell lines and primary human trophoblasts were cultured with varying Na+ concentrations. RESULTS: Women with preeclampsia had reduced placental and urinary Na+ concentrations, yet increased urinary angiotensinogen and reduced active renin, aldosterone concentrations, and osmotic response signal TonEBP (tonicity-responsive enhancer binding protein) expression. In trophoblast cell cultures, TonEBP was consistently increased upon augmented Na+ exposure. Mechanistically, inhibiting Na+/K+-ATPase or adding mannitol evoked the TonEBP response, whereas inhibition of cytoskeletal signaling abolished it. CONCLUSIONS: Enhanced Na+ availability induced osmotic gradient-dependent cytoskeletal signals in trophoblasts, resulting in proangiogenic responses. As placental salt availability is compromised in preeclampsia, adverse systemic responses are thus conceivable.
KW - adenosine triphosphatases
KW - biopsy
KW - preeclampsia
KW - sodium
KW - trophoblasts
UR - http://www.scopus.com/inward/record.url?scp=85197749783&partnerID=8YFLogxK
U2 - 10.1161/HYPERTENSIONAHA.124.23001
DO - 10.1161/HYPERTENSIONAHA.124.23001
M3 - Article
C2 - 38966986
AN - SCOPUS:85197749783
SN - 0194-911X
VL - 81
SP - 1924
EP - 1934
JO - Hypertension
JF - Hypertension
IS - 9
ER -