Placental Vesicles Carry Active Endothelial Nitric Oxide Synthase and Their Activity is Reduced in Preeclampsia

Preeclampsia, a multisystem hypertensive disorder of pregnancy, is associated with increased systemic vascular resistance. Placentae from patients with preeclampsia have reduced levels of endothelial nitric oxide synthase (eNOS) and, thus, less nitric oxide (NO). Syncytiotrophoblast extracellular ve...

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Bibliographic Details
Published in:Hypertension (Dallas, Tex. 1979) Tex. 1979), 2017-08, Vol.70 (2), p.372-381
Main Authors: Motta-Mejia, Carolina, Kandzija, Neva, Zhang, Wei, Mhlomi, Vuyane, Cerdeira, Ana Sofia, Burdujan, Alexandra, Tannetta, Dionne, Dragovic, Rebecca, Sargent, Ian L, Redman, Christopher W, Kishore, Uday, Vatish, Manu
Format: Article
Language:English
Subjects:
Adult
Blood Pressure Determination - methods
Cells, Cultured
Extracellular Vesicles - physiology
Female
Humans
Hypertension - diagnosis
Hypertension - etiology
Nitric Oxide - metabolism
Nitric Oxide Synthase Type III - metabolism
Original
Pre-Eclampsia - metabolism
Pre-Eclampsia - pathology
Pre-Eclampsia - physiopathology
Pregnancy
Statistics as Topic
Trophoblasts - pathology
Trophoblasts - physiology
Vascular Resistance - physiology
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Summary:Preeclampsia, a multisystem hypertensive disorder of pregnancy, is associated with increased systemic vascular resistance. Placentae from patients with preeclampsia have reduced levels of endothelial nitric oxide synthase (eNOS) and, thus, less nitric oxide (NO). Syncytiotrophoblast extracellular vesicles (STBEV), comprising microvesicles (STBMV) and exosomes, carry signals from the syncytiotrophoblast to the mother. We hypothesized that STBEV-bound eNOS (STBEV-eNOS), capable of producing NO, are released into the maternal circulation. Dual-lobe ex vivo placental perfusion and differential centrifugation was used to isolate STBEV from preeclampsia (n=8) and normal pregnancies (NP; n=11). Plasma samples of gestational age-matched preeclampsia and NP (n=6) were used to isolate circulating STBMV. STBEV expressed placental alkaline phosphatase, confirming placental origin. STBEV coexpressed eNOS, but not inducible nitric oxide synthase, confirmed using Western blot, flow cytometry, and immunodepletion. STBEV-eNOS produced NO, which was significantly inhibited by   -nitro-l-arginine methyl ester (eNOS inhibitor;
ISSN:0194-911X
1524-4563
DOI:10.1161/HYPERTENSIONAHA.117.09321