Placental syncytiotrophoblast extracellular vesicles enter primary endothelial cells through clathrin-mediated endocytosis
(2020) In Placenta 100. p.133-141- Abstract
Introduction: The aim was to investigate syncytiotrophoblast extracellular vesicle (STBEV) uptake mechanisms by primary endothelial cells, the effects on gene expression, cell activation as well as the effect of aspirin. Methods: The STBEVs were derived using the placental perfusion system, from normal or preeclamptic placentas. Endothelial uptake was analysed with flow cytometry. To elucidate uptake, different inhibitors were tested; Cytochalasin D, Chlorpromazine hydrochloride, Methyl-B-cyclodextrin, Dynasore and Wortmannin. Endothelial gene expression was evaluated using an endothelial cell biology qPCR array. Cell activation was studied by ICAM-1 surface expression after STBEV exposure, with and without aspirin treatment. Results:... (More)
Introduction: The aim was to investigate syncytiotrophoblast extracellular vesicle (STBEV) uptake mechanisms by primary endothelial cells, the effects on gene expression, cell activation as well as the effect of aspirin. Methods: The STBEVs were derived using the placental perfusion system, from normal or preeclamptic placentas. Endothelial uptake was analysed with flow cytometry. To elucidate uptake, different inhibitors were tested; Cytochalasin D, Chlorpromazine hydrochloride, Methyl-B-cyclodextrin, Dynasore and Wortmannin. Endothelial gene expression was evaluated using an endothelial cell biology qPCR array. Cell activation was studied by ICAM-1 surface expression after STBEV exposure, with and without aspirin treatment. Results: Normal and preeclamptic STBEV uptake was blocked in similar ways. Chlorpromazine, Dynasore and Wortmannin almost completely blocked STBEV uptake. Methyl-B-cyclodextrin blocked 45–60% of the uptake while Cytochalasin D did not block uptake at all. Neither normal nor preeclamptic STBEVs had any significant effects on endothelial gene expression. Normal STBEVs down-regulated cell surface protein ICAM-1 expression, with and without aspirin treatment. Aspirin had no effect on STBEV uptake or cellular gene expression on its own, however it down regulated ICAM-1 protein expression in combination with preeclamptic STBEV exposure. Discussion: STBEV uptake primarily occurred through clathrin-mediated endocytosis. The STBEVs had no significant effect on gene expression but did have effects on ICAM-1 surface expression. The prophylactic mechanisms of aspirin may be by preventing the endothelium from being activated by the preeclamptic STBEVs.
(Less)
- author
- Cronqvist, Tina LU ; Erlandsson, Lena LU ; Tannetta, Dionne and Hansson, Stefan R. LU
- organization
- publishing date
- 2020-10
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Endocytosis, Endothelial cells, Preeclampsia, Syncytiotrophoblast extracellular vesicles, Vesicular uptake
- in
- Placenta
- volume
- 100
- pages
- 9 pages
- publisher
- W.B. Saunders
- external identifiers
-
- pmid:32980046
- scopus:85087962378
- ISSN
- 0143-4004
- DOI
- 10.1016/j.placenta.2020.07.006
- language
- English
- LU publication?
- yes
- id
- 765bdd92-8536-4959-b688-4190616dd82d
- date added to LUP
- 2020-07-30 10:35:34
- date last changed
- 2024-06-12 18:07:21
@article{765bdd92-8536-4959-b688-4190616dd82d, abstract = {{<p>Introduction: The aim was to investigate syncytiotrophoblast extracellular vesicle (STBEV) uptake mechanisms by primary endothelial cells, the effects on gene expression, cell activation as well as the effect of aspirin. Methods: The STBEVs were derived using the placental perfusion system, from normal or preeclamptic placentas. Endothelial uptake was analysed with flow cytometry. To elucidate uptake, different inhibitors were tested; Cytochalasin D, Chlorpromazine hydrochloride, Methyl-B-cyclodextrin, Dynasore and Wortmannin. Endothelial gene expression was evaluated using an endothelial cell biology qPCR array. Cell activation was studied by ICAM-1 surface expression after STBEV exposure, with and without aspirin treatment. Results: Normal and preeclamptic STBEV uptake was blocked in similar ways. Chlorpromazine, Dynasore and Wortmannin almost completely blocked STBEV uptake. Methyl-B-cyclodextrin blocked 45–60% of the uptake while Cytochalasin D did not block uptake at all. Neither normal nor preeclamptic STBEVs had any significant effects on endothelial gene expression. Normal STBEVs down-regulated cell surface protein ICAM-1 expression, with and without aspirin treatment. Aspirin had no effect on STBEV uptake or cellular gene expression on its own, however it down regulated ICAM-1 protein expression in combination with preeclamptic STBEV exposure. Discussion: STBEV uptake primarily occurred through clathrin-mediated endocytosis. The STBEVs had no significant effect on gene expression but did have effects on ICAM-1 surface expression. The prophylactic mechanisms of aspirin may be by preventing the endothelium from being activated by the preeclamptic STBEVs.</p>}}, author = {{Cronqvist, Tina and Erlandsson, Lena and Tannetta, Dionne and Hansson, Stefan R.}}, issn = {{0143-4004}}, keywords = {{Endocytosis; Endothelial cells; Preeclampsia; Syncytiotrophoblast extracellular vesicles; Vesicular uptake}}, language = {{eng}}, pages = {{133--141}}, publisher = {{W.B. Saunders}}, series = {{Placenta}}, title = {{Placental syncytiotrophoblast extracellular vesicles enter primary endothelial cells through clathrin-mediated endocytosis}}, url = {{http://dx.doi.org/10.1016/j.placenta.2020.07.006}}, doi = {{10.1016/j.placenta.2020.07.006}}, volume = {{100}}, year = {{2020}}, }