Antiphospholipid antibodies induce proinflammatory and procoagulant pathways in endothelial cells

Markos Patsouras; Eirini Alexopoulou; Spyros Foutadakis; Eirini Tsiki; Panagiota Karagianni; Marios Agelopoulos; Panayiotis G Vlachoyiannopoulos

doi:10.1016/j.jtauto.2023.100202

Antiphospholipid antibodies induce proinflammatory and procoagulant pathways in endothelial cells

J Transl Autoimmun. 2023 May 2:6:100202. doi: 10.1016/j.jtauto.2023.100202. eCollection 2023.

Authors

Markos Patsouras¹, Eirini Alexopoulou¹, Spyros Foutadakis², Eirini Tsiki¹, Panagiota Karagianni¹, Marios Agelopoulos², Panayiotis G Vlachoyiannopoulos¹

Affiliations

¹ Department of Pathophysiology, Medical School, National and Kapodistrian University of Athens, Greece.
² Center of Basic Research, Biomedical Research Foundation, Academy of Athens, 4 Soranou Ephessiou Street, Athens, 11527, Greece.

Abstract

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.

Keywords: Antiphospholipid syndrome (APS); Computational biology tools; Gene expression programs; Inflammatory and procoagulant phenotype; Transcriptional regulators; Transcriptomics analysis.