CD146⁺ endothelial and pericyte populations define a repair-associated neovascularization program in rheumatoid arthritis pannus

Rheumatoid arthritis (RA) pannus is characterized by extensive neovascularization, yet the cellular programs underlying this process remain incompletely understood. We investigated CD146⁺ synovial populations using bulk and single-cell RNA sequencing in the collagen-induced chronic polyarthritis model of D1BC transgenic mice, combined with comparative analyses of published human RA datasets. Bulk RNA sequencing identified CD146 as a marker of endothelial and perivascular populations enriched for angiogenic signatures. Single-cell analysis revealed four endothelial subsets defined by Apln and Aplnr expression, including Apln ⁺, Aplnr ⁺, Apln ⁺/ Aplnr ⁺, and double-negative populations. These subsets exhibited transcriptional features consistent with repair-associated capillary programs and showed similarities to endothelial states described during pulmonary capillary regeneration. Ligand-receptor and gene ontology analyses indicated active endothelial-pericyte communication associated with neovascularization. A distinct CD146⁺ pericyte population expressing Cspg4 , but lacking Acta2 and Pdgfrb , preferentially interacted with Apln ⁺ and Aplnr ⁺ endothelial subsets. Immunohistochemistry confirmed the spatial association of NG2⁺ pericytes with CD31⁺ neovessels within pannus tissue. These findings identify distinct CD146⁺ endothelial and pericyte populations that characterize repair-associated neovascularization in rheumatoid arthritis pannus and provide insight into vascular remodeling in chronic synovial inflammation.