Endothelial Dysfunction in Severe Preeclampsia is Mediated by Soluble Factors, Rather than Extracellular Vesicles

Abstract In severe early-onset preeclampsia (sPE) the placenta releases soluble angiogenesis-regulating proteins, trophoblast-derived fragments, and extracellular vesicles (EVs). Their relative importance in disease pathogenesis is not presently understood. We explanted placental villi from healthy...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Michelle O’Brien, Dora Baczyk, John C. Kingdom
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ce71d337a43243dfbeb1905bb7b80474
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:ce71d337a43243dfbeb1905bb7b80474
record_format	dspace
spelling	oai:doaj.org-article:ce71d337a43243dfbeb1905bb7b804742021-12-02T12:32:43ZEndothelial Dysfunction in Severe Preeclampsia is Mediated by Soluble Factors, Rather than Extracellular Vesicles10.1038/s41598-017-06178-z2045-2322https://doaj.org/article/ce71d337a43243dfbeb1905bb7b804742017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06178-zhttps://doaj.org/toc/2045-2322Abstract In severe early-onset preeclampsia (sPE) the placenta releases soluble angiogenesis-regulating proteins, trophoblast-derived fragments, and extracellular vesicles (EVs). Their relative importance in disease pathogenesis is not presently understood. We explanted placental villi from healthy and sPE women then separated the media into: total-conditioned, EV-depleted and EV-enriched media. Three fractions were compared for; angiogenic protein secretion by ELISA, angiogenic and inflammation gene mRNA expression and leukocyte adhesion assay. sPE placental villi secreted significantly less PlGF (70 ± 18 pg/mL) than preterm controls (338 ± 203; p = 0.03). sFlt-1:PlGF ratios in total-conditioned (115 ± 29) and EV-depleted media (136 ± 40) from sPE placental villi were significantly higher than in EV-enriched media (42 ± 12; p < 0.01) or any preterm or term media. Fluorescent-labeled EVs derived across normal gestation, but not from sPE, actively entered HUVECs. From sPE placental villi, the soluble fraction, but not EV-enriched fraction, significantly repressed angiogenesis (0.83 ± 0.05 fold, p = 0.02), induced HO-1 mRNA (15.3 ± 5.1 fold, p < 0.05) and induced leukocyte adhesion (2.2 ± 0.4 fold, p = 0.04). Soluble media (total-conditioned and EV-depleted media) from sPE placental villi induced endothelial dysfunction in HUVEC, while the corresponding EV-enriched fraction showed no such effects. Our data suggest that soluble factors including angiogenesis-regulating proteins, dominate the vascular pathology of this disease.Michelle O’BrienDora BaczykJohn C. KingdomNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Michelle O’Brien Dora Baczyk John C. Kingdom Endothelial Dysfunction in Severe Preeclampsia is Mediated by Soluble Factors, Rather than Extracellular Vesicles
description	Abstract In severe early-onset preeclampsia (sPE) the placenta releases soluble angiogenesis-regulating proteins, trophoblast-derived fragments, and extracellular vesicles (EVs). Their relative importance in disease pathogenesis is not presently understood. We explanted placental villi from healthy and sPE women then separated the media into: total-conditioned, EV-depleted and EV-enriched media. Three fractions were compared for; angiogenic protein secretion by ELISA, angiogenic and inflammation gene mRNA expression and leukocyte adhesion assay. sPE placental villi secreted significantly less PlGF (70 ± 18 pg/mL) than preterm controls (338 ± 203; p = 0.03). sFlt-1:PlGF ratios in total-conditioned (115 ± 29) and EV-depleted media (136 ± 40) from sPE placental villi were significantly higher than in EV-enriched media (42 ± 12; p < 0.01) or any preterm or term media. Fluorescent-labeled EVs derived across normal gestation, but not from sPE, actively entered HUVECs. From sPE placental villi, the soluble fraction, but not EV-enriched fraction, significantly repressed angiogenesis (0.83 ± 0.05 fold, p = 0.02), induced HO-1 mRNA (15.3 ± 5.1 fold, p < 0.05) and induced leukocyte adhesion (2.2 ± 0.4 fold, p = 0.04). Soluble media (total-conditioned and EV-depleted media) from sPE placental villi induced endothelial dysfunction in HUVEC, while the corresponding EV-enriched fraction showed no such effects. Our data suggest that soluble factors including angiogenesis-regulating proteins, dominate the vascular pathology of this disease.
format	article
author	Michelle O’Brien Dora Baczyk John C. Kingdom
author_facet	Michelle O’Brien Dora Baczyk John C. Kingdom
author_sort	Michelle O’Brien
title	Endothelial Dysfunction in Severe Preeclampsia is Mediated by Soluble Factors, Rather than Extracellular Vesicles
title_short	Endothelial Dysfunction in Severe Preeclampsia is Mediated by Soluble Factors, Rather than Extracellular Vesicles
title_full	Endothelial Dysfunction in Severe Preeclampsia is Mediated by Soluble Factors, Rather than Extracellular Vesicles
title_fullStr	Endothelial Dysfunction in Severe Preeclampsia is Mediated by Soluble Factors, Rather than Extracellular Vesicles
title_full_unstemmed	Endothelial Dysfunction in Severe Preeclampsia is Mediated by Soluble Factors, Rather than Extracellular Vesicles
title_sort	endothelial dysfunction in severe preeclampsia is mediated by soluble factors, rather than extracellular vesicles
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/ce71d337a43243dfbeb1905bb7b80474
work_keys_str_mv	AT michelleobrien endothelialdysfunctioninseverepreeclampsiaismediatedbysolublefactorsratherthanextracellularvesicles AT dorabaczyk endothelialdysfunctioninseverepreeclampsiaismediatedbysolublefactorsratherthanextracellularvesicles AT johnckingdom endothelialdysfunctioninseverepreeclampsiaismediatedbysolublefactorsratherthanextracellularvesicles
_version_	1718394006785753088

Endothelial Dysfunction in Severe Preeclampsia is Mediated by Soluble Factors, Rather than Extracellular Vesicles

Ejemplares similares