Alterations of Placental Sodium in Preeclampsia: Trophoblast Responses

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

Y1 - 2024/9

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 - https://www.scopus.com/pages/publications/85197749783

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 -