Mistry, Hiten DHiten DMistryKlossner, RahelRahelKlossner0000-0003-1615-156XScaife, Paula JPaula JScaifeEisele, NicoleNicoleEiseleKurlak, Lesia OLesia OKurlakKallol, Sampada ArvindraoSampada ArvindraoKallolAlbrecht, ChristianeChristianeAlbrechtGennari, CarineCarineGennari0000-0001-7386-5935Briggs, Louise VLouise VBriggsBroughton Pipkin, FionaFionaBroughton PipkinMohaupt, MarkusMarkusMohaupt2024-10-262024-10-262024-09https://boris-portal.unibe.ch/handle/20.500.12422/178786BACKGROUND 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.enadenosine triphosphatases biopsy preeclampsia sodium trophoblasts600 - Technology::610 - Medicine & health500 - Science::570 - Life sciences; biologyarticle10.48350/1985633896698610.1161/HYPERTENSIONAHA.124.23001