Syncytiotrophoblast derived extracellular vesicles transfer functional placental miRNAs to primary human endothelial cells
Cronqvist, Tina LU ; Tannetta, Dionne ; Mörgelin, Matthias LU ; Belting, Mattias LU ; Sargent, Ian I. L. ; Familari, Mary LU and Hansson, Stefan R. LU
(2017)
In Scientific Reports
7(1).
- Abstract
During the pregnancy associated syndrome preeclampsia (PE), there is increased release of placental syncytiotrophoblast extracellular vesicles (STBEVs) and free foetal haemoglobin (HbF) into the maternal circulation. In the present study we investigated the uptake of normal and PE STBEVs by primary human coronary artery endothelial cells (HCAEC) and the effects of free HbF on this uptake. Our results show internalization of STBEVs into primary HCAEC, and transfer of placenta specific miRNAs from STBEVs into the endoplasmic reticulum and mitochondria of these recipient cells. Further, the transferred miRNAs were functional, causing a down regulation of specific target genes, including the PE associated gene fms related tyrosine kinase 1... (More)
During the pregnancy associated syndrome preeclampsia (PE), there is increased release of placental syncytiotrophoblast extracellular vesicles (STBEVs) and free foetal haemoglobin (HbF) into the maternal circulation. In the present study we investigated the uptake of normal and PE STBEVs by primary human coronary artery endothelial cells (HCAEC) and the effects of free HbF on this uptake. Our results show internalization of STBEVs into primary HCAEC, and transfer of placenta specific miRNAs from STBEVs into the endoplasmic reticulum and mitochondria of these recipient cells. Further, the transferred miRNAs were functional, causing a down regulation of specific target genes, including the PE associated gene fms related tyrosine kinase 1 (FLT1). When co-Treating normal STBEVs with HbF, the miRNA deposition is altered from the mitochondria to the ER and the cell membrane becomes ruffled, as was also seen with PE STBEVs. These findings suggest that STBEVs may cause endothelial damage and contribute to the endothelial dysfunction typical for PE. The miRNA mediated effects on gene expression may contribute to the oxidative and endoplasmic reticulum stress described in PE, as well as endothelial reprogramming that may underlay the increased risk of cardiovascular disease reported for women with PE later in life.
(Less)
- author
- Cronqvist, Tina
LU
; Tannetta, Dionne
; Mörgelin, Matthias
LU
; Belting, Mattias
LU
; Sargent, Ian I. L.
; Familari, Mary
LU
and Hansson, Stefan R.
LU
- organization
- publishing date
- 2017-12-01
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Scientific Reports
- volume
- 7
- issue
- 1
- article number
- 4558
- publisher
- Nature Publishing Group
- external identifiers
-
- scopus:85021748952
- pmid:28676635
- wos:000404654400004
- ISSN
- 2045-2322
- DOI
- 10.1038/s41598-017-04468-0
- language
- English
- LU publication?
- yes
- id
- 7c7f6a99-8ff0-4801-ba08-3b0053c73ff7
- date added to LUP
- 2017-07-18 10:34:46
- date last changed
- 2024-05-12 17:27:32
@article{7c7f6a99-8ff0-4801-ba08-3b0053c73ff7,
abstract = {{<p>During the pregnancy associated syndrome preeclampsia (PE), there is increased release of placental syncytiotrophoblast extracellular vesicles (STBEVs) and free foetal haemoglobin (HbF) into the maternal circulation. In the present study we investigated the uptake of normal and PE STBEVs by primary human coronary artery endothelial cells (HCAEC) and the effects of free HbF on this uptake. Our results show internalization of STBEVs into primary HCAEC, and transfer of placenta specific miRNAs from STBEVs into the endoplasmic reticulum and mitochondria of these recipient cells. Further, the transferred miRNAs were functional, causing a down regulation of specific target genes, including the PE associated gene fms related tyrosine kinase 1 (FLT1). When co-Treating normal STBEVs with HbF, the miRNA deposition is altered from the mitochondria to the ER and the cell membrane becomes ruffled, as was also seen with PE STBEVs. These findings suggest that STBEVs may cause endothelial damage and contribute to the endothelial dysfunction typical for PE. The miRNA mediated effects on gene expression may contribute to the oxidative and endoplasmic reticulum stress described in PE, as well as endothelial reprogramming that may underlay the increased risk of cardiovascular disease reported for women with PE later in life.</p>}},
author = {{Cronqvist, Tina and Tannetta, Dionne and Mörgelin, Matthias and Belting, Mattias and Sargent, Ian I. L. and Familari, Mary and Hansson, Stefan R.}},
issn = {{2045-2322}},
language = {{eng}},
month = {{12}},
number = {{1}},
publisher = {{Nature Publishing Group}},
series = {{Scientific Reports}},
title = {{Syncytiotrophoblast derived extracellular vesicles transfer functional placental miRNAs to primary human endothelial cells}},
url = {{http://dx.doi.org/10.1038/s41598-017-04468-0}},
doi = {{10.1038/s41598-017-04468-0}},
volume = {{7}},
year = {{2017}},
}