Antiphospholipid antibodies induce proinflammatory and procoagulant pathways in endothelial cells

Antiphospholipid syndrome (APS) is an autoimmune thrombophilia characterized by recurrent thrombotic events and/or pregnancy morbidity in the presence of antiphospholipid antibodies detected either as anti-cardiolipin, anti-β2 Glycoprotein I (anti-β2GPI) or Lupus anticoagulant (LA). Endothelial dere...

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Main Authors: Markos Patsouras, Eirini Alexopoulou, Spyros Foutadakis, Eirini Tsiki, Panagiota Karagianni, Marios Agelopoulos, Panayiotis G. Vlachoyiannopoulos
Format: Article
Language:English
Published: Elsevier 2023-01-01
Series:Journal of Translational Autoimmunity
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2589909023000151
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author Markos Patsouras
Eirini Alexopoulou
Spyros Foutadakis
Eirini Tsiki
Panagiota Karagianni
Marios Agelopoulos
Panayiotis G. Vlachoyiannopoulos
author_facet Markos Patsouras
Eirini Alexopoulou
Spyros Foutadakis
Eirini Tsiki
Panagiota Karagianni
Marios Agelopoulos
Panayiotis G. Vlachoyiannopoulos
author_sort Markos Patsouras
collection DOAJ
description Antiphospholipid syndrome (APS) is an autoimmune thrombophilia characterized by recurrent thrombotic events and/or pregnancy morbidity in the presence of antiphospholipid antibodies detected either as anti-cardiolipin, anti-β2 Glycoprotein I (anti-β2GPI) or Lupus anticoagulant (LA). Endothelial deregulation characterizes the syndrome. To address gene expression changes accompanying the development of autoimmune phenotype in endothelial cells in the context of APS, we performed transcriptomics analysis in Human Umbilical Vein Endothelial Cells (HUVECs) stimulated with IgG from APS patients and β2GPI, followed by intersection of RNA-seq data with published microarray and ChIP-seq results (Chromatin Immunoprecipitation). Our strategy revealed that during HUVEC activation diverse signaling pathways such as TNF-α, TGF-β, MAPK38, and Hippo are triggered as indicated by Gene Ontology (GO) classification and pathway analysis. Finally, cell biology approaches performed side-by-side in naïve and stimulated cultured HUVECs, as well as, in placenta specimens derived from Healthy donors (HDs) and APS-patients verified the evolution of an APS-characteristic gene expression program in endothelial cells during the initial stages of the disease's development.
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spelling doaj.art-e42b1d353c8f4335bd63426067af42082023-06-19T04:29:19ZengElsevierJournal of Translational Autoimmunity2589-90902023-01-016100202Antiphospholipid antibodies induce proinflammatory and procoagulant pathways in endothelial cellsMarkos Patsouras0Eirini Alexopoulou1Spyros Foutadakis2Eirini Tsiki3Panagiota Karagianni4Marios Agelopoulos5Panayiotis G. Vlachoyiannopoulos6Department of Pathophysiology, Medical School, National and Kapodistrian University of Athens, GreeceDepartment of Pathophysiology, Medical School, National and Kapodistrian University of Athens, GreeceCenter of Basic Research, Biomedical Research Foundation, Academy of Athens, 4 Soranou Ephessiou Street, Athens, 11527, GreeceDepartment of Pathophysiology, Medical School, National and Kapodistrian University of Athens, GreeceDepartment of Pathophysiology, Medical School, National and Kapodistrian University of Athens, GreeceCenter of Basic Research, Biomedical Research Foundation, Academy of Athens, 4 Soranou Ephessiou Street, Athens, 11527, GreeceDepartment of Pathophysiology, Medical School, National and Kapodistrian University of Athens, Greece; Corresponding author. Department of Pathophysiology, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias str, 11527, Athens, Greece.Antiphospholipid syndrome (APS) is an autoimmune thrombophilia characterized by recurrent thrombotic events and/or pregnancy morbidity in the presence of antiphospholipid antibodies detected either as anti-cardiolipin, anti-β2 Glycoprotein I (anti-β2GPI) or Lupus anticoagulant (LA). Endothelial deregulation characterizes the syndrome. To address gene expression changes accompanying the development of autoimmune phenotype in endothelial cells in the context of APS, we performed transcriptomics analysis in Human Umbilical Vein Endothelial Cells (HUVECs) stimulated with IgG from APS patients and β2GPI, followed by intersection of RNA-seq data with published microarray and ChIP-seq results (Chromatin Immunoprecipitation). Our strategy revealed that during HUVEC activation diverse signaling pathways such as TNF-α, TGF-β, MAPK38, and Hippo are triggered as indicated by Gene Ontology (GO) classification and pathway analysis. Finally, cell biology approaches performed side-by-side in naïve and stimulated cultured HUVECs, as well as, in placenta specimens derived from Healthy donors (HDs) and APS-patients verified the evolution of an APS-characteristic gene expression program in endothelial cells during the initial stages of the disease's development.http://www.sciencedirect.com/science/article/pii/S2589909023000151Antiphospholipid syndrome (APS)Transcriptomics analysisComputational biology toolsInflammatory and procoagulant phenotypeTranscriptional regulatorsGene expression programs
spellingShingle Markos Patsouras
Eirini Alexopoulou
Spyros Foutadakis
Eirini Tsiki
Panagiota Karagianni
Marios Agelopoulos
Panayiotis G. Vlachoyiannopoulos
Antiphospholipid antibodies induce proinflammatory and procoagulant pathways in endothelial cells
Journal of Translational Autoimmunity
Antiphospholipid syndrome (APS)
Transcriptomics analysis
Computational biology tools
Inflammatory and procoagulant phenotype
Transcriptional regulators
Gene expression programs
title Antiphospholipid antibodies induce proinflammatory and procoagulant pathways in endothelial cells
title_full Antiphospholipid antibodies induce proinflammatory and procoagulant pathways in endothelial cells
title_fullStr Antiphospholipid antibodies induce proinflammatory and procoagulant pathways in endothelial cells
title_full_unstemmed Antiphospholipid antibodies induce proinflammatory and procoagulant pathways in endothelial cells
title_short Antiphospholipid antibodies induce proinflammatory and procoagulant pathways in endothelial cells
title_sort antiphospholipid antibodies induce proinflammatory and procoagulant pathways in endothelial cells
topic Antiphospholipid syndrome (APS)
Transcriptomics analysis
Computational biology tools
Inflammatory and procoagulant phenotype
Transcriptional regulators
Gene expression programs
url http://www.sciencedirect.com/science/article/pii/S2589909023000151
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