Placental Syncytiotrophoblast-Derived Extracellular Vesicles Carry Active NEP (Neprilysin) and Are Increased in Preeclampsia

NEP (neprilysin) is a widely expressed membrane-bound metalloprotease, which binds and cleaves a variety of peptides including vasodilators, natriuretics, and diuretics. Higher levels of NEP result in hypertension—a cardinal feature of the placental disease preeclampsia. Syncytiotrophoblast-derived...

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Bibliographic Details
Published in:Hypertension (Dallas, Tex. 1979) Tex. 1979), 2019-05, Vol.73 (5), p.1112-1119
Main Authors: Gill, Manjot, Motta-Mejia, Carolina, Kandzija, Neva, Cooke, William, Zhang, Wei, Cerdeira, Ana Sofia, Bastie, Claire, Redman, Christopher, Vatish, Manu
Format: Article
Language:English
Subjects:
Adult
Blood Pressure - physiology
Blotting, Western
Extracellular Vesicles - metabolism
Extracellular Vesicles - pathology
Female
Flow Cytometry
Humans
Immunohistochemistry
Neprilysin - biosynthesis
Placenta - metabolism
Placenta - pathology
Pre-Eclampsia - metabolism
Pre-Eclampsia - pathology
Pre-Eclampsia - physiopathology
Pregnancy
Trophoblasts - metabolism
Trophoblasts - pathology
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Summary:NEP (neprilysin) is a widely expressed membrane-bound metalloprotease, which binds and cleaves a variety of peptides including vasodilators, natriuretics, and diuretics. Higher levels of NEP result in hypertension—a cardinal feature of the placental disease preeclampsia. Syncytiotrophoblast-derived extracellular vesicles (EVs), comprising microvesicles and exosomes, are released into the peripheral circulation in pregnancy and are postulated as a key mechanism coupling placental dysfunction and maternal phenotype in preeclampsia. We aimed to determine whether higher levels of active NEP are found in syncytiotrophoblast-derived EVs in preeclampsia compared with normal pregnancy. Using immunostaining and Western blotting, we first demonstrated that NEP levels are greater not only in preeclampsia placental tissue but also in syncytiotrophoblast-derived microvesicles and exosomes isolated from preeclampsia placentas (P
ISSN:0194-911X
1524-4563
DOI:10.1161/HYPERTENSIONAHA.119.12707