HRS Degradation-Induced Nicotinamide Deficiency in Placental Extracellular Vesicles Triggers Preeclampsia by Disrupting Maternal-Fetal Immune Homeostasis.

ABSTRACT: Preeclampsia (PE) is closely associated with alterations in placental extracellular vesicles (pEVs), but the mechanisms and their role in PE pathogenesis remain unclear. This study reveals that nicotinamide (NAM) levels in PE-derived pEVs (PE-EVs) are lower than in pEVs from normal pregnancies, correlating with disease severity. Functionally, NAM in pEVs inhibits Th1 differentiation via SIRT1 suppression and Th17 differentiation via macrophages. NAM-deficient pEVs exhibit reduced capacity to inhibit Th1 and Th17 cell differentiation both in vitro and in vivo, leading to PE-like symptoms. NAM is enriched in pEVs compared to placental villous tissue and maternal serum. The lower NAM in PE-EVs is due to decreased hepatocyte growth factor-regulated tyrosine kinase substrate (HRS) expression in

SUBMITTER: Fei H 

PROVIDER: S-EPMC12931225 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature