Cargando…
Syncytiotrophoblast extracellular vesicles impair rat uterine vascular function via the lectin-like oxidized LDL receptor-1
Syncytiotrophoblast extracellular vesicles (STBEVs) are placenta derived particles that are released into the maternal circulation during pregnancy. Abnormal levels of STBEVs have been proposed to affect maternal vascular function. The lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1)...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5495440/ https://www.ncbi.nlm.nih.gov/pubmed/28672042 http://dx.doi.org/10.1371/journal.pone.0180364 |
_version_ | 1783247807004540928 |
---|---|
author | Spaans, Floor Kao, Cindy K. Morton, Jude S. Quon, Anita L. Sawamura, Tatsuya Tannetta, Dionne S. Sargent, Ian L. Davidge, Sandra T. |
author_facet | Spaans, Floor Kao, Cindy K. Morton, Jude S. Quon, Anita L. Sawamura, Tatsuya Tannetta, Dionne S. Sargent, Ian L. Davidge, Sandra T. |
author_sort | Spaans, Floor |
collection | PubMed |
description | Syncytiotrophoblast extracellular vesicles (STBEVs) are placenta derived particles that are released into the maternal circulation during pregnancy. Abnormal levels of STBEVs have been proposed to affect maternal vascular function. The lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is a multi-ligand scavenger receptor. Increased LOX-1 expression and activation has been proposed to contribute to endothelial dysfunction. As LOX-1 has various ligands, we hypothesized that, being essentially packages of lipoproteins, STBEVs are able to activate the LOX-1 receptor thereby impairing vascular function via the production of superoxide and decreased nitric oxide bioavailability. Uterine arteries were obtained in late gestation from Sprague-Dawley rats and incubated for 24h with or without human STBEVs (derived from a normal pregnant placenta) in the absence or presence of a LOX-1 blocking antibody. Vascular function was assessed using wire myography. Endothelium-dependent maximal vasodilation to methylcholine was impaired by STBEVs (MCh E(max): 57.7±5.9% in STBEV-incubated arteries vs. 77.8±2.9% in controls, p<0.05). This was prevented by co-incubation of STBEV-incubated arteries with LOX-1 blocking antibodies (MCh E(max): 78.8±4.3%, p<0.05). Pre-incubation of the vessels with a nitric oxide synthase inhibitor (L-NAME) demonstrated that the STBEV-induced impairment in vasodilation was due to decreased nitric oxide contribution (ΔAUC 12.2±11.7 in STBEV-arteries vs. 86.5±20 in controls, p<0.05), which was abolished by LOX-1 blocking antibody (ΔAUC 98.9±17, p<0.05). In STBEV-incubated vessels, LOX-1 inhibition resulted in an increased endothelial nitric oxide synthase expression (p<0.05), to a level similar to control vessels. The oxidant scavenger, superoxide dismutase, did not improve this impairment, nor were vascular superoxide levels altered. Our data support an important role for STBEVs in impairment of vascular function via activation of LOX-1 and reduced nitric oxide mediated vasodilation. Moreover, we postulate that the LOX-1 pathway could be a potential therapeutic target in pathologies associated with vascular dysfunction during pregnancy. |
format | Online Article Text |
id | pubmed-5495440 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-54954402017-07-18 Syncytiotrophoblast extracellular vesicles impair rat uterine vascular function via the lectin-like oxidized LDL receptor-1 Spaans, Floor Kao, Cindy K. Morton, Jude S. Quon, Anita L. Sawamura, Tatsuya Tannetta, Dionne S. Sargent, Ian L. Davidge, Sandra T. PLoS One Research Article Syncytiotrophoblast extracellular vesicles (STBEVs) are placenta derived particles that are released into the maternal circulation during pregnancy. Abnormal levels of STBEVs have been proposed to affect maternal vascular function. The lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is a multi-ligand scavenger receptor. Increased LOX-1 expression and activation has been proposed to contribute to endothelial dysfunction. As LOX-1 has various ligands, we hypothesized that, being essentially packages of lipoproteins, STBEVs are able to activate the LOX-1 receptor thereby impairing vascular function via the production of superoxide and decreased nitric oxide bioavailability. Uterine arteries were obtained in late gestation from Sprague-Dawley rats and incubated for 24h with or without human STBEVs (derived from a normal pregnant placenta) in the absence or presence of a LOX-1 blocking antibody. Vascular function was assessed using wire myography. Endothelium-dependent maximal vasodilation to methylcholine was impaired by STBEVs (MCh E(max): 57.7±5.9% in STBEV-incubated arteries vs. 77.8±2.9% in controls, p<0.05). This was prevented by co-incubation of STBEV-incubated arteries with LOX-1 blocking antibodies (MCh E(max): 78.8±4.3%, p<0.05). Pre-incubation of the vessels with a nitric oxide synthase inhibitor (L-NAME) demonstrated that the STBEV-induced impairment in vasodilation was due to decreased nitric oxide contribution (ΔAUC 12.2±11.7 in STBEV-arteries vs. 86.5±20 in controls, p<0.05), which was abolished by LOX-1 blocking antibody (ΔAUC 98.9±17, p<0.05). In STBEV-incubated vessels, LOX-1 inhibition resulted in an increased endothelial nitric oxide synthase expression (p<0.05), to a level similar to control vessels. The oxidant scavenger, superoxide dismutase, did not improve this impairment, nor were vascular superoxide levels altered. Our data support an important role for STBEVs in impairment of vascular function via activation of LOX-1 and reduced nitric oxide mediated vasodilation. Moreover, we postulate that the LOX-1 pathway could be a potential therapeutic target in pathologies associated with vascular dysfunction during pregnancy. Public Library of Science 2017-07-03 /pmc/articles/PMC5495440/ /pubmed/28672042 http://dx.doi.org/10.1371/journal.pone.0180364 Text en © 2017 Spaans et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Spaans, Floor Kao, Cindy K. Morton, Jude S. Quon, Anita L. Sawamura, Tatsuya Tannetta, Dionne S. Sargent, Ian L. Davidge, Sandra T. Syncytiotrophoblast extracellular vesicles impair rat uterine vascular function via the lectin-like oxidized LDL receptor-1 |
title | Syncytiotrophoblast extracellular vesicles impair rat uterine vascular function via the lectin-like oxidized LDL receptor-1 |
title_full | Syncytiotrophoblast extracellular vesicles impair rat uterine vascular function via the lectin-like oxidized LDL receptor-1 |
title_fullStr | Syncytiotrophoblast extracellular vesicles impair rat uterine vascular function via the lectin-like oxidized LDL receptor-1 |
title_full_unstemmed | Syncytiotrophoblast extracellular vesicles impair rat uterine vascular function via the lectin-like oxidized LDL receptor-1 |
title_short | Syncytiotrophoblast extracellular vesicles impair rat uterine vascular function via the lectin-like oxidized LDL receptor-1 |
title_sort | syncytiotrophoblast extracellular vesicles impair rat uterine vascular function via the lectin-like oxidized ldl receptor-1 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5495440/ https://www.ncbi.nlm.nih.gov/pubmed/28672042 http://dx.doi.org/10.1371/journal.pone.0180364 |
work_keys_str_mv | AT spaansfloor syncytiotrophoblastextracellularvesiclesimpairratuterinevascularfunctionviathelectinlikeoxidizedldlreceptor1 AT kaocindyk syncytiotrophoblastextracellularvesiclesimpairratuterinevascularfunctionviathelectinlikeoxidizedldlreceptor1 AT mortonjudes syncytiotrophoblastextracellularvesiclesimpairratuterinevascularfunctionviathelectinlikeoxidizedldlreceptor1 AT quonanital syncytiotrophoblastextracellularvesiclesimpairratuterinevascularfunctionviathelectinlikeoxidizedldlreceptor1 AT sawamuratatsuya syncytiotrophoblastextracellularvesiclesimpairratuterinevascularfunctionviathelectinlikeoxidizedldlreceptor1 AT tannettadionnes syncytiotrophoblastextracellularvesiclesimpairratuterinevascularfunctionviathelectinlikeoxidizedldlreceptor1 AT sargentianl syncytiotrophoblastextracellularvesiclesimpairratuterinevascularfunctionviathelectinlikeoxidizedldlreceptor1 AT davidgesandrat syncytiotrophoblastextracellularvesiclesimpairratuterinevascularfunctionviathelectinlikeoxidizedldlreceptor1 |