Differences in Endothelial Activation and Dysfunction Induced by Antiphospholipid Antibodies Among Groups of Patients With Thrombotic, Refractory, and Non-refractory Antiphospholipid Syndrome
Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by pregnancy morbidity or thrombosis and persistent antiphospholipid antibodies (aPL) that bind to the endothelium and induce endothelial activation, which is evidenced by the expression of adhesion molecules and the production...
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Frontiers Media S.A.
2021
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oai:doaj.org-article:6dda233c52a8468f88b3e54908534d062021-12-02T11:34:25ZDifferences in Endothelial Activation and Dysfunction Induced by Antiphospholipid Antibodies Among Groups of Patients With Thrombotic, Refractory, and Non-refractory Antiphospholipid Syndrome1664-042X10.3389/fphys.2021.764702https://doaj.org/article/6dda233c52a8468f88b3e54908534d062021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphys.2021.764702/fullhttps://doaj.org/toc/1664-042XAntiphospholipid syndrome (APS) is an autoimmune disorder characterized by pregnancy morbidity or thrombosis and persistent antiphospholipid antibodies (aPL) that bind to the endothelium and induce endothelial activation, which is evidenced by the expression of adhesion molecules and the production of reactive oxygen species (ROS) and subsequent endothelial dysfunction marked by a decrease in the synthesis and release of nitric oxide (NO). These endothelial alterations are the key components for the development of severe pathological processes in APS. Patients with APS can be grouped according to the presence of other autoimmune diseases (secondary APS), thrombosis alone (thrombotic APS), pregnancy morbidity (obstetric APS), and refractoriness to conventional treatment regimens (refractory APS). Typically, patients with severe and refractory obstetric APS exhibit thrombosis and are classified as those having primary or secondary APS. The elucidation of the mechanisms underlying these alterations according to the different groups of patients with APS could help establish new therapies, particularly necessary for severe and refractory cases. Therefore, this study aimed to evaluate the differences in endothelial activation and dysfunction induced by aPL between patients with refractory obstetric APS and other APS clinical manifestations. Human umbilical vein endothelial cells (HUVECs) were stimulated with polyclonal immunoglobulin-G (IgG) from different groups of patients n = 21), including those with primary (VTI) and secondary thrombotic APS (VTII) and refractory primary (RI+), refractory secondary (RII+), and non-refractory primary (NR+) obstetric APS. All of them with thrombosis. The expression of adhesion molecules; the production of ROS, NO, vascular endothelial growth factor (VEGF), and endothelin-1; and the generation of microparticles were used to evaluate endothelial activation and dysfunction. VTI IgG induced the expression of adhesion molecules and the generation of microparticles and VEGF. RI+ IgG induced the expression of adhesion molecules and decreased NO production. RII+ IgG increased the production of microparticles, ROS, and endothelin-1 and reduced NO release. NR+ IgG increased the production of microparticles and endothelin-1 and decreased the production of VEGF and NO. These findings reveal differences in endothelial activation and dysfunction among groups of patients with APS, which should be considered in future studies to evaluate new therapies, especially in refractory cases.Manuela VelásquezLuisa F. PeláezMauricio RojasRaúl Narváez-SánchezJesús A. VelásquezCarlos EscuderoCarlos EscuderoCarlos EscuderoSebastián San MartínSebastián San MartínSebastián San MartínÁngela P. CadavidÁngela P. CadavidÁngela P. CadavidFrontiers Media S.A.articleantiphospholipid syndromeendothelial cellsendothelial activation and dysfunctionbeta 2-glycoprotein Iimmunoglobulin Gantiphosholipid syndromePhysiologyQP1-981ENFrontiers in Physiology, Vol 12 (2021) |
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| topic |
antiphospholipid syndrome endothelial cells endothelial activation and dysfunction beta 2-glycoprotein I immunoglobulin G antiphosholipid syndrome Physiology QP1-981 |
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antiphospholipid syndrome endothelial cells endothelial activation and dysfunction beta 2-glycoprotein I immunoglobulin G antiphosholipid syndrome Physiology QP1-981 Manuela Velásquez Luisa F. Peláez Mauricio Rojas Raúl Narváez-Sánchez Jesús A. Velásquez Carlos Escudero Carlos Escudero Carlos Escudero Sebastián San Martín Sebastián San Martín Sebastián San Martín Ángela P. Cadavid Ángela P. Cadavid Ángela P. Cadavid Differences in Endothelial Activation and Dysfunction Induced by Antiphospholipid Antibodies Among Groups of Patients With Thrombotic, Refractory, and Non-refractory Antiphospholipid Syndrome |
| description |
Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by pregnancy morbidity or thrombosis and persistent antiphospholipid antibodies (aPL) that bind to the endothelium and induce endothelial activation, which is evidenced by the expression of adhesion molecules and the production of reactive oxygen species (ROS) and subsequent endothelial dysfunction marked by a decrease in the synthesis and release of nitric oxide (NO). These endothelial alterations are the key components for the development of severe pathological processes in APS. Patients with APS can be grouped according to the presence of other autoimmune diseases (secondary APS), thrombosis alone (thrombotic APS), pregnancy morbidity (obstetric APS), and refractoriness to conventional treatment regimens (refractory APS). Typically, patients with severe and refractory obstetric APS exhibit thrombosis and are classified as those having primary or secondary APS. The elucidation of the mechanisms underlying these alterations according to the different groups of patients with APS could help establish new therapies, particularly necessary for severe and refractory cases. Therefore, this study aimed to evaluate the differences in endothelial activation and dysfunction induced by aPL between patients with refractory obstetric APS and other APS clinical manifestations. Human umbilical vein endothelial cells (HUVECs) were stimulated with polyclonal immunoglobulin-G (IgG) from different groups of patients n = 21), including those with primary (VTI) and secondary thrombotic APS (VTII) and refractory primary (RI+), refractory secondary (RII+), and non-refractory primary (NR+) obstetric APS. All of them with thrombosis. The expression of adhesion molecules; the production of ROS, NO, vascular endothelial growth factor (VEGF), and endothelin-1; and the generation of microparticles were used to evaluate endothelial activation and dysfunction. VTI IgG induced the expression of adhesion molecules and the generation of microparticles and VEGF. RI+ IgG induced the expression of adhesion molecules and decreased NO production. RII+ IgG increased the production of microparticles, ROS, and endothelin-1 and reduced NO release. NR+ IgG increased the production of microparticles and endothelin-1 and decreased the production of VEGF and NO. These findings reveal differences in endothelial activation and dysfunction among groups of patients with APS, which should be considered in future studies to evaluate new therapies, especially in refractory cases. |
| format |
article |
| author |
Manuela Velásquez Luisa F. Peláez Mauricio Rojas Raúl Narváez-Sánchez Jesús A. Velásquez Carlos Escudero Carlos Escudero Carlos Escudero Sebastián San Martín Sebastián San Martín Sebastián San Martín Ángela P. Cadavid Ángela P. Cadavid Ángela P. Cadavid |
| author_facet |
Manuela Velásquez Luisa F. Peláez Mauricio Rojas Raúl Narváez-Sánchez Jesús A. Velásquez Carlos Escudero Carlos Escudero Carlos Escudero Sebastián San Martín Sebastián San Martín Sebastián San Martín Ángela P. Cadavid Ángela P. Cadavid Ángela P. Cadavid |
| author_sort |
Manuela Velásquez |
| title |
Differences in Endothelial Activation and Dysfunction Induced by Antiphospholipid Antibodies Among Groups of Patients With Thrombotic, Refractory, and Non-refractory Antiphospholipid Syndrome |
| title_short |
Differences in Endothelial Activation and Dysfunction Induced by Antiphospholipid Antibodies Among Groups of Patients With Thrombotic, Refractory, and Non-refractory Antiphospholipid Syndrome |
| title_full |
Differences in Endothelial Activation and Dysfunction Induced by Antiphospholipid Antibodies Among Groups of Patients With Thrombotic, Refractory, and Non-refractory Antiphospholipid Syndrome |
| title_fullStr |
Differences in Endothelial Activation and Dysfunction Induced by Antiphospholipid Antibodies Among Groups of Patients With Thrombotic, Refractory, and Non-refractory Antiphospholipid Syndrome |
| title_full_unstemmed |
Differences in Endothelial Activation and Dysfunction Induced by Antiphospholipid Antibodies Among Groups of Patients With Thrombotic, Refractory, and Non-refractory Antiphospholipid Syndrome |
| title_sort |
differences in endothelial activation and dysfunction induced by antiphospholipid antibodies among groups of patients with thrombotic, refractory, and non-refractory antiphospholipid syndrome |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/6dda233c52a8468f88b3e54908534d06 |
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