Endothelial dysfunction in APS: advancing pathophysiological understanding to improve management

Endothelial dysfunction (ED) is a hallmark of antiphospholipid syndrome (APS) driven by chronic antiphospholipid antibody (aPL) exposure. Beyond acute thrombotic events, ED contributes to atherosclerosis, vascular remodelling, stenosis and multi-organ manifestations, positioning the endothelium as a putative target for disease monitoring and therapeutic intervention. In this review, we integrate new experimental and clinical studies with emerging data presented at recent international meetings that advance our understanding of endothelial pathophysiology in APS. These studies reveal novel APS vascular endotypes and convergence between aPL-driven endothelial thromboinflammation, endothelial-to-mesenchymal transition, extracellular matrix remodelling and aberrant cell growth pathways across arterial, venous and capillary territories, and multiple organs. We discuss evolving approaches to assess endothelial health, including circulating biomarkers, endothelial colony-forming cells, and non-invasive functional and imaging-based tools. Finally, we highlight the need to integrate early detection, aggressive cardiovascular risk modification and precision medicine to mitigate ED and improve long-term outcomes in APS.