Investigating the role of Endothelial Dysfunction in Antiphospholipid Syndrome by using Patient-Specific Endothelial Colony-Forming Cells

Background Antiphospholipid syndrome (APS) is a prothrombotic autoimmune disease that occurs as primary condition (PAPS) or associated with other disease(s). APS diagnosis requires at least one clinical criterion (thrombosis and/or pregnancy morbidity) in the presence of antiphospholipid antibodies (aPLs). APS clinical manifestations are associated with endothelial dysfunction (ED). Whether ED is only a consequence of the aPL-endothelium interaction, or is also a susceptibility factor of the host it is an aspect poorly investigated. In this context, patient-specific endothelial colony-forming cells (ECFCs) are a valuable tool to investigate ED. Objective To assess ED in PAPS patients and disclose the pathway(s) responsible for ED. Methods ECFCs were isolated from PAPS patients, aPL carriers and healthy controls1. The presence of ED was investigated assessing ECFC phenotype and ability to promote thrombosis2. Plasmatic levels of soluble ED markers were measured in the same subjects. Results Although ECFCs were isolated with similar efficiency in the analyzed groups, only in PAPS ECFCs the presence of constitutive ED was observed. Specifically, PAPS ECFCs promoted a faster thrombin generation in thrombin generation assay, and were characterized by higher expression of the adhesion molecule VCAM-1 and the pro-coagulant molecule tissue factor. ED in PAPS patients was confirmed by the increased plasmatic levels of the soluble form of VCAM-1, ICAM-1, PECAM-1, E-Selectin. Conclusions Our findings indicate the presence of constitutive ED in PAPS patients, suggesting ED involvement in APS-related thrombosis. Ongoing studies seek to expand our understanding of constitutive and aPL-related ED in PAPS patients and the underlying mechanism(s) involved. References 1. Colombo E, Calcaterra F, Cappelletti M, Mavilio D, Della Bella S. Comparison of Fibronectin and Collagen in Supporting the Isolation and Expansion of Endothelial Progenitor Cells from Human Adult Peripheral Blood. PLoS One. 2013 Jun 18;8(6):e66734. doi: 10.1371/journal.pone.0066734. 2. Bacci M, Cancellara A, Ciceri R, Romualdi E, Pessi V, Tumminello F, Fantuzzi M, Donadini MP, Lodigiani C, Della Bella S, Calcaterra F, Mavilio D. Development of Personalized Thrombogenesis and Thrombin Generation Assays to Assess Endothelial Dysfunction in Cardiovascular Diseases. Biomedicines. 2023 Jun 8;11(6):1669. doi: 10.3390/biomedicines11061669.