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Endothelial activation and injury by microparticles in patients with systemic lupus erythematosus and rheumatoid arthritis
BACKGROUND: Endothelial activation and damage is commonly observed in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) and is related to development of atherosclerosis and cardiovascular diseases. Different components of the immune system seem to participate in the endo...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6343289/ https://www.ncbi.nlm.nih.gov/pubmed/30674349 http://dx.doi.org/10.1186/s13075-018-1796-4 |
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author | Atehortúa, Laura Rojas, Mauricio Vásquez, Gloria Muñoz-Vahos, Carlos H. Vanegas-García, Adriana Posada-Duque, Rafael Andrés Castaño, Diana |
author_facet | Atehortúa, Laura Rojas, Mauricio Vásquez, Gloria Muñoz-Vahos, Carlos H. Vanegas-García, Adriana Posada-Duque, Rafael Andrés Castaño, Diana |
author_sort | Atehortúa, Laura |
collection | PubMed |
description | BACKGROUND: Endothelial activation and damage is commonly observed in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) and is related to development of atherosclerosis and cardiovascular diseases. Different components of the immune system seem to participate in the endothelial injury, such as generation of autoantibodies and formation of immune complexes (ICs). Microparticles (MPs) and their immune complexes (MPs-ICs) are increased in the circulation of patients with SLE and RA; therefore, we propose these extracellular vesicles could interact and modulate the function of endothelial cells. Hence, the effect of MPs and MPs-ICs from patients with SLE and RA in endothelial cells was evaluated. METHODS: Macrovascular and microvascular endothelial cells were exposed to MPs and MPs-ICs from healthy donors and patients with SLE and RA. Vesicles uptake/binding, expression of adhesion molecules, cytokine and chemokine production, monocyte adherence, and alterations of endothelial monolayer were evaluated by flow cytometry and fluorescence microscopy. RESULTS: Endothelial cells internalized MPs and MPs-ICs and increased CD54 and CD102 expression and CCL2, CCL5, and IL-6 production after the treatment with these extracellular vesicles, which led to an increase in the adherence of classic monocytes. These vesicles also induced low expression of VE-cadherin in membrane, depolymerization of actin filaments, and formation of intercellular spaces, which led to endothelial death and increased permeability after MPs and MPs-ICs exposure. CONCLUSIONS: MPs and MPs-ICs from patients with SLE and RA increase adhesion molecules expression, chemokine production, and structural alterations in macrovascular and microvascular endothelial cells. Therefore, high counts of these vesicles in patients would promote endothelial alterations and secondary tissue leukocyte infiltration. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13075-018-1796-4) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6343289 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-63432892019-01-24 Endothelial activation and injury by microparticles in patients with systemic lupus erythematosus and rheumatoid arthritis Atehortúa, Laura Rojas, Mauricio Vásquez, Gloria Muñoz-Vahos, Carlos H. Vanegas-García, Adriana Posada-Duque, Rafael Andrés Castaño, Diana Arthritis Res Ther Research Article BACKGROUND: Endothelial activation and damage is commonly observed in patients with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) and is related to development of atherosclerosis and cardiovascular diseases. Different components of the immune system seem to participate in the endothelial injury, such as generation of autoantibodies and formation of immune complexes (ICs). Microparticles (MPs) and their immune complexes (MPs-ICs) are increased in the circulation of patients with SLE and RA; therefore, we propose these extracellular vesicles could interact and modulate the function of endothelial cells. Hence, the effect of MPs and MPs-ICs from patients with SLE and RA in endothelial cells was evaluated. METHODS: Macrovascular and microvascular endothelial cells were exposed to MPs and MPs-ICs from healthy donors and patients with SLE and RA. Vesicles uptake/binding, expression of adhesion molecules, cytokine and chemokine production, monocyte adherence, and alterations of endothelial monolayer were evaluated by flow cytometry and fluorescence microscopy. RESULTS: Endothelial cells internalized MPs and MPs-ICs and increased CD54 and CD102 expression and CCL2, CCL5, and IL-6 production after the treatment with these extracellular vesicles, which led to an increase in the adherence of classic monocytes. These vesicles also induced low expression of VE-cadherin in membrane, depolymerization of actin filaments, and formation of intercellular spaces, which led to endothelial death and increased permeability after MPs and MPs-ICs exposure. CONCLUSIONS: MPs and MPs-ICs from patients with SLE and RA increase adhesion molecules expression, chemokine production, and structural alterations in macrovascular and microvascular endothelial cells. Therefore, high counts of these vesicles in patients would promote endothelial alterations and secondary tissue leukocyte infiltration. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13075-018-1796-4) contains supplementary material, which is available to authorized users. BioMed Central 2019-01-23 2019 /pmc/articles/PMC6343289/ /pubmed/30674349 http://dx.doi.org/10.1186/s13075-018-1796-4 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Atehortúa, Laura Rojas, Mauricio Vásquez, Gloria Muñoz-Vahos, Carlos H. Vanegas-García, Adriana Posada-Duque, Rafael Andrés Castaño, Diana Endothelial activation and injury by microparticles in patients with systemic lupus erythematosus and rheumatoid arthritis |
title | Endothelial activation and injury by microparticles in patients with systemic lupus erythematosus and rheumatoid arthritis |
title_full | Endothelial activation and injury by microparticles in patients with systemic lupus erythematosus and rheumatoid arthritis |
title_fullStr | Endothelial activation and injury by microparticles in patients with systemic lupus erythematosus and rheumatoid arthritis |
title_full_unstemmed | Endothelial activation and injury by microparticles in patients with systemic lupus erythematosus and rheumatoid arthritis |
title_short | Endothelial activation and injury by microparticles in patients with systemic lupus erythematosus and rheumatoid arthritis |
title_sort | endothelial activation and injury by microparticles in patients with systemic lupus erythematosus and rheumatoid arthritis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6343289/ https://www.ncbi.nlm.nih.gov/pubmed/30674349 http://dx.doi.org/10.1186/s13075-018-1796-4 |
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