Human blood vessel organoids recapitulate key mechanisms of transition from vasculopathy to fibrosis in systemic sclerosis - PubMed
3 hours ago
- #Blood Vessel Organoids
- #Fibrosis
- #Systemic Sclerosis
- Systemic sclerosis (SSc) transitions from vasculopathy to fibrosis, but mechanisms are poorly understood.
- Blood vessel organoids (BVOs) from SSc patients and healthy controls were used to model vasculopathy.
- SSc serum exposure caused angiogenic defects, endothelial-to-mesenchymal transition (EndMT), and fibrosis-related gene upregulation.
- Epigenetic and proteomic profiling confirmed EndMT and shifts in endothelial-pericyte interactions.
- SSc IgG autoantibodies were implicated in endothelial injury; depletion restored vascular structure.
- Bosentan and γ-secretase inhibitor DAPT partially reversed vascular abnormalities and EndMT markers.
- BVOs serve as a multiomic model for SSc vasculopathy and potential therapy evaluation.
- Notch/γ-secretase inhibition is identified as a novel therapeutic target for SSc vasculopathy.