Microvascular Endothelial Cells License Antiphospholipid Syndrome (APS) Vasculopathy Through YAP1- and CCN2-Mediated Signaling
Authors' conclusion
This study revealed activation of YAP1-mediated signaling in APS dermal microvessels and demonstrated that the YAP1 target CCN2 plays a role in facilitating pro-proliferative communication between MVECs and vascular smooth muscle cells.
Study context
- Population
- Patients with APS complicated by livedo racemosa (skin biopsies) and APS nephropathy (kidney biopsies); healthy dermal microvascular endothelial cells (MVECs); mouse model of APS immunoglobulin G (IgG)-accelerated neointima formation
Main finding
As reported in the abstract
- Increased endothelial CCN1 and CCN2 expression by single-cell RNA sequencing, confirmed in APS skin by microscopy and in APS plasma by ELISA
- Patient IgG upregulated CCN1 and CCN2 in healthy MVECs via Toll-like receptor 4- and YAP1-mediated signaling
- CCN2 from APS IgG-stimulated MVECs led to vascular smooth muscle cell proliferation and migration, inhibited by anti-CCN2 antibody or EGFR depletion
- Increased CCN2 expression with YAP1 nuclear translocation in kidney vessels of APS nephropathy biopsies
- Anti-CCN2 monoclonal antibody significantly reduced neointima thickening and cell proliferation in mouse model
Original publication
Microvascular Endothelial Cells License APS Vasculopathy Through YAP1- and CCN2-Mediated Signaling. Circulation. Published 29 August 2025. doi:10.
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