Serum from Patients with Antiphospholipid Syndrome Differentially Affects Venous and Microcirculatory Endothelial...

Antiphospholipid syndrome is a systemic autoimmune disease characterized by elevated circulating antiphospholipid antibodies and a predisposition to recurrent venous and arterial thrombosis. The underlying pathophysiology of antiphospholipid syndrome remains under active investigation, with endothelial dysfunction recognized as a key contributor to vascular complications. In this study, we showed that serum from antiphospholipid syndrome patients differentially affects distinct endothelial cell types, leading to variations in migration and angiogenic behavior. Using human umbilical vein endothelial cells and human microvascular endothelial cells, we assessed the biological response to serum exposure. Treatment with antiphospholipid syndrome serum was associated with an enhanced angiogenic phenotype in venous endothelium, with a significant increase in two of the four tubulogenesis parameters assessed and a trend towards increased migration, while microvascular endothelium remained largely unaffected. Consistently, metalloproteinase-9 activity was upregulated, with these effects being more pronounced in venous compared to microvascular endothelium. Moreover, caspase-3 activity remained unchanged, suggesting that caspase-3-dependent apoptosis is unlikely to be a major contributor to the endothelial response observed under these conditions. These results enhance our understanding of the pathogenesis and highlight the distinct endothelial responses to the antiphospholipid environment. Further investigation into the underlying mechanisms may facilitate the development of targeted therapeutic strategies to mitigate vascular complications.